Genotype, Serotype and Supertype Classification

Table of genotypes, serotypes and supertypes

Find below a table (Table 1) showing the currently available human leucocyte antigen (HLA) class I and II serotypes and genotypes, as well as the HLA class I supertypes that have been defined.

Alleles, chromosomes and genotypes

An individual's genotype for a gene is the set of alleles, which the gene contains. In a diploid organism, one that has two copies of each chromosome, two alleles make up the individual's genotype. An allele is the specification of a gene that is located at a particular position (locus) on a chromosome. Put differently, the two copies of the gene in diploid organisms are the alleles. The fact that, in diploid organisms, a gene exists in two copies makes for possible variations in phenotype, the expressed characteristics (e.g. blue or brown eyes). An organism in which the two copies of the gene are identical, i.e. have the same allele, is called homozygous for that gene. An organism, which has two different alleles of the gene, is called heterozygous.

How serotypes are defined

HLA genes that encode immune-associated glycoproteins are located on chromosome 6p21. HLA class I and II genes are known to be highly polymorphic, i.e. they exist in many different forms among humans. HLA class I and II genes are individually found at HLA-A, -B and -C and well as HLA-DR, -DQ and -DP loci. The initial discovery of HLA gene products was made in the late 1960s by observing that serum samples from transplanted patients exhibit reactivities against lymphoid cells of other subjects. The actual definition of HLA serotypes was established through a series of refined analyses of these earlier results in combination with the use of antiserum panels that exhibit greater specificities against HLA molecules. This method requires to have the right antibodies to the HLA proteins. Sero means antibody here. Therefore, a HLA serotype is the HLA protein (expressed from the respective HLA gene) that is detected by the respective antibody which is available. Because antibodies to HLA class I or II proteins do not exist in similar versatile numbers and/or are not detected easily, the number of HLA serotypes is less than the number of associated genotypes.

At the moment, antibodies to many HLA class I proteins are reliable, i.e. they are specific for particular HLA class I proteins. Reliable antibodies to HLA class II proteins are not easily available, but most HLA class II genes are also defined as serotypes today (see Table 1 below). Despite the advances in defining HLA serotypes, a given HLA serotype represents only a rough collection of proteins expressed by the respective HLA gene. In addition, some serotypes still exhibit cross-reactivity towards other serotypes. Such examples are found among HLA-A9, -23 and -24.

Genotyping DNA sequences

Due to the uniqueness of individual DNA sequences, probes and primers complementary to HLA genes have been used for genotyping of both HLA class I and II genes. The Sequence Specific Oligonucleotide Probes (SSOP) method has been used for genotyping of HLA-class II genes and for finding alleles that exist in HLA class I serotypes. On this basis, many of the sequences of the HLA class I and II locus were found to consist of multiple families of alleles, which have been grouped e.g. into the HLA-A2 family. Within HLA-A2, there are at least 25 genotypes, i.e. at least 25 HLA class I (A2) genes are different. So, a HLA class I or II genotype is one particular HLA form defined by its DNA sequence.

What are supertypes?

The principle function of HLA class I and II molecules are to present antigenic peptides derived from intracellular processing of native proteins to CD8+ and CD4+ lymphocytes. Binding patterns obtained from studies of individual HLA class I molecules have revealed that some of them within a given allele family share binding specificities towards the same panel of peptides. This property is reflected by some common structural features of the peptide-binding grooves of these HLA class I molecules, which accommodate these peptides. The collection of HLA class I molecules that exhibit this property is designated as a supertype. Under this structural classification, a few HLA class I supertypes are defined for the numerous allele family that are now known to exist.

References

The composition of serotype equivalents is due to Schreuder GM, Hurley CK, Marsh SG, et al. HLA dictionary 2004: summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens. Hum Immunol 2005. 66(2):170-210. The supertype classification is from Sette A, Sidney J. Nine major HLA Class I supertypes account for the vast preponderance of HLA-A and -B polymorphism. Immunogenetics 1999. 50(3-4):201-212.

Table 1. Genotypes, serotypes and supertypes

Genotype Serotype Supertype
A*01 A1  
A*0101 A1 A1
A*0102 A1 A1
A*0201 A2 A2
A*01011, A*02012
A*0202 A2 A2
A*0203 A203 A2
A*0204 A2 A2
A*0205 A2 A2
A*0206 A2 A2
A*0207 A2 A2
A*0208 A2  
A*0209 A2  
A*0210 A210  
A*0211 A2  
A*0212 A2  
A*0213 A2  
A*0214 A2  
A*02142
A*0216 A2  
A*0217 A2  
A*01171, A*02172    
A*0218 A2  
A*0220 A2  
A*0221 A2  
A*0222 A2  
A*0224 A2  
A*0225 A2  
A*0229 A2  
A*03 A3  
A*0301 A3 A3
A*03011, A*03012,
A*03013
A*0302 A3  
A*0304 A3  
A*1101 A11 A3
A*1102 A11  
A*1103 A11  
A*1104 A11  
A*1105 A11  
A*2301 A23(9) A24
A*24 A24(9)  
A*2402 A24(9) A24
A*2402101, A*24021102L,
A*24022
A*2403 A2403 A24
A*2404 A24(9) A24
A*2405 A24(9)  
A*2406 A24(9)  
A*2407 A24(9)  
A*2408 A24(9)  
A*2413 A24(9)  
A*2414 A24(9)  
A*2501 A25(10) A1
A*2601 A26(10) A1
A*2602 A26(10)  
A*2603 A26(10)  
A*2604 A10 A1
A*2605 A26(10)  
A*2606 A26(10)  
A*2607 A26(10)  
A*2608 A26(10)  
A*2610 A10  
A*2901 A29(19)  
A*2902 A29(19)  
A*3001 A30(19) A24
A*3002 A30(19) A24
A*3003 A30(19) A24
A*3004 A30(19)  
A*3101 A31(19) A3
A*31012
A*3201 A32(19) A1
A*3202 A32(19)  
A*3301 A33(19) A3
A*3303 A33(19)  
A*3401 A34(10)  
A*3402 A34(10)  
A*3601 A36 A1
A*4301 A43 A1
A*6601 A66(10)  
A*6602 A66(10)  
A*6801 A68(28) A3
A*68011, A*68012
A*6802 A68(28) A2
A*6803 A28  
A*68031, A*68032  
A*6808 A68(28)  
A*6901 A69(28) A2
A*7401 A74(19)  
A*7402 A74(19)  
A*7403 A19  
A*8001 A80 A1
B*07 B*07  
B*0702 B7 B7
B*07021, B*07022,
B*07023
B*0703 B703 B7
B*0704 B7 B7
B*0705 B7 B7
B*0706 B7  
B*0707 B7  
B*0709 B7  
B*0711 B7  
B*08 B*08  
B*0801 B8  
B*0802 B8  
B*0803 B8  
B*0806 B8  
B*1301 B13 B62
B*1302 B13 B62
B*14 B*14  
B*1401 B64(14) B27
B*1402 B65(14) B27
B*1501 B62(15) B62
B*1501101, B*15012
B*1502 B75(15) B62
B*1503 B72(70) B27
B*1504 B62(15)  
B*1505 B62(15)  
B*1506 B62(15) B62
B*1507 B62(15)  
B*1508 B75(15) B7
B*1509 B70 B27
B*1510 B71(70) B27
B*1511 B75(15)  
B*1512 B76(15) B62
B*1513 B77(15) B62
B*1514 B76(15) B62
B*1515 B62(15)  
B*1516 B63(15) B58
B*1517 B63(15) B58
B*1518 B71(70) B27
B*1519 B76(15) B62
B*1521 B75(15) B62
B*1522 B35  
B*1524 B62(15)  
B*1525 B62(15)  
B*1527 B62(15)  
B*1528 B15  
B*1529 B15  
B*1530 B75(15)  
B*1531 B75(15)  
B*1532 B62(15)  
B*1533 B15  
B*1534 B15  
B*1535 B15  
B*1545 B62(15)  
B*1546 B72(70)  
B*1548 B62(15)  
B*18 B*18 B44
B*1801 B18  
B*1802 B18  
B*1803 B18  
B*1805 B18  
B*1806 B18  
B*27 B*27  
B*2701 B27 B27
B*2702 B27 B27
B*2703 B27 B27
B*2704 B27 B27
B*2705 B27 B27
B*27052, B*27053
B*2706 B27 B27
B*2707 B27 B27
B*2708   B27
B*2709 B27  
B*2710 B27  
B*2711 B27  
B*2712 B27  
B*2713 B27  
B*35 B*35  
B*3501 B35 B7
B*3502 B35 B7
B*3503 B35 B7
B*3504 B35  
B*3505 B35  
B*3506 B35  
B*3507 B35  
B*3508 B35  
B*3509 B35  
B*35091, B*35092    
B*3511 B35  
B*3512 B35  
B*3513 B35  
B*3514 B35  
B*3515 B35  
B*3517 B35  
B*3518 B35  
B*3519 B35  
B*3520 B35  
B*3526 B35  
B*3527 B35  
B*3701 B*37 B44
B*3702 B*37  
B*3801 B38(16) B27
B*3802 B38(16) B27
B*38021, B*38022
B*3803 B16  
B*3901 B3901 B27
B*39011, B*39013
B*3902 B3902 B27
B*39031, B*39022
B*3903 B39(16) B27
B*3904 B39(16) B27
B*3905 B39(16)  
B*3906 B39(16)  
B*39061, B*39062    
B*3908 B39(16)  
B*3909 B39(16)  
B*3910 B39(16)  
B*3912 B39(16)  
B*3913 B39(16)  
B*40 B40  
B*4001 B60(40) B44
B*4002 B61(40)  
B*4003 B60(40)  
B*4004 B40  
B*4005 B4005  
B*4006 B61(40) B44
B*4009 B61(40)  
B*4010 B60(40)  
B*4011 B40  
B*4012 B40  
B*4016 B61(40)  
B*4101 B41 B44
B*4102 B41  
B*4201 B42  
B*4202 B42  
B*44 B44(12)  
B*4402 B44(12) B44
B*4403 B44(12) B44
B*44031, B*44032
B*4404 B44(12)  
B*4405 B44(12)  
B*4406 B44(12)  
B*4407 B44(12)  
B*4408 B44(12)  
B*4409 B12  
B*4501 B45(12) B44
B*4601 B46 B62
B*4701 B47  
B*4702 B47  
B*4801 B48 B27
B*4802 B48 B27
B*4805 B48  
B*4901 B49(21) B44
B*5001 B50(21) B44
B*51   B7
B*5101 B51(5)  
B*51011, B*51012    
B*5102 B5102  
B*51021, B*51022    
B*5103 B5103  
B*5104 B53like  
B*5105 B51(5)  
B*5106 B5  
B*5107 B51(5)  
B*5108 B51(5)  
B*5109 B51(5)  
B*5116 B52(5)  
B*52   B62
B*5201 B52(5)  
B*52011, B*52012    
B*5301 B53 B7
B*5401 B54(22) B7
B*5501 B55(22) B7
B*5502 B55(22) B7
B*5503 B67  
B*5504 B55(22)  
B*5505 B22  
B*5507 B54(22)  
B*5601 B56(22) B7
B*5602 B56(22) B7
B*5604 B56(22)  
B*5701 B57(17) B58
B*5702 B57(17) B58
B*5703 B57(17)  
B*5704 B57(17)  
B*58   B58
B*5801 B58(17)  
B*5802 B58(17)  
B*5901 B59  
B*6701 B67 B7
B*67011, B*67012
B*7301 B73 B27
B*7801 B78 B7
B*7802 B78  
B*78021, B*78022    
B*8101 B81  
B*8201 B822x45  
Cw*0102 Cw1  
Cw*0103 Cw1  
Cw*0104    
Cw*0202 Cw2  
Cw*02021, Cw*02022,
Cw*02023, Cw*02024
   
Cw*0203    
Cw*0204    
Cw*0301 Name abandoned  
Cw*0302 Cw10(w3)  
Cw*0303 Cw9(w3)  
Cw*03031, Cw*03032    
Cw*0304 Cw10(w3)  
Cw*03041, Cw*03042 Cw10(w3)  
Cw*0305    
Cw*0306    
Cw*0307 Cw3  
Cw*0308    
Cw*0309 Cw3  
Cw*0310 Cw3  
Cw*0311    
Cw*0312    
Cw*0401 Cw4  
Cw*04011, Cw*04012 Cw4  
Cw*0402 Cw4  
Cw*0403    
Cw*0404    
Cw*0405    
Cw*0406    
Cw*0407    
Cw*0408    
Cw*0501 Cw5  
Cw*0502 Cw5  
Cw*0503    
Cw*0504    
Cw*0601 Name abandoned  
Cw*0602 Cw6  
Cw*0603    
Cw*0604    
Cw*0605 Cw6  
Cw*0606    
Cw*0607    
Cw*0701 Cw7  
Cw*0702 Cw7  
Cw*0703    
Cw*0704 Cw7  
Cw*0705    
Cw*0706 Cw7  
Cw*0707    
Cw*0708    
Cw*0709    
Cw*0710    
Cw*0711    
Cw*0712 Cw7  
Cw*0713    
Cw*0714 Cw7  
Cw*0801 Cw8  
Cw*0802 Cw8  
Cw*0803 Cw8  
Cw*0804 Cw8  
Cw*0805    
Cw*0806    
Cw*0807    
Cw*0808    
Cw*0809    
Cw*1202    
Cw*1203    
Cw*1204    
Cw*1205    
Cw*1206    
Cw*1207    
Cw*1301    
Cw*1402    
Cw*1403    
Cw*1404    
Cw*1502    
Cw*1503    
Cw*1504    
Cw*1505    
Cw*1506    
Cw*1507    
Cw*1508    
Cw*1509    
Cw*1510    
Cw*1601    
Cw*1602    
Cw*1604    
Cw*1701    
Cw*1702    
Cw*1703    
Cw*1801    
Cw*1802    
DPA1*0102/DPB1*0201 DPw2  
DPA1*0103/DPB1*0201 DPw2  
DPA1*0201/DPB1*0401 DPw4  
DPA1*0201/DPB1*0901    
DPB1*0101 DPw1  
DPB1*01011, DPB1*01012    
DPB1*0201 DPw2  
DPB1*02012, DPB1*01013    
DPB1*0301 DPw3  
DPB1*0401 DPw4  
DPB1*0402 DPw4  
DPB1*0501 DPw5  
DPB1*0601 DPw6  
DQA1*0101/DQB1*0501 DQ5(1)  
DQA1*0102/DQB1*0602 DQ6(1)  
DQA1*0301/DQB1*0301 DQ7(3)  
DQA1*0301/DQB1*0302 DQ8(3)  
DQA1*0501/DQB1*0201 DQ2  
DQA1*0501/DQB1*0301 DQ7(3)  
DQB1*0201 DQ2  
DQB1*0203 DQ2  
DQB1*0301 DQ7(3)  
DQB1*03011, DQB1*03012    
DQB1*0302 DQ8(3)  
DQB1*03032 DQ9(3)  
DQB1*0304 DQ7(3)  
DQB1*0306 DQ3  
DQB1*0401 DQ4  
DQB1*0402 DQ4  
DQB1*0501 DQ5(1)  
DQB1*0502 DQ5(1)  
DQB1*0503 DQ5(1)  
DQB1*05031, DQB1*05032    
DQB1*0601 DQ6(1)  
DQB1*06011, DQB1*06012,
DQB1*06013
   
DQB1*0602 DQ6(1)  
DQB1*0603 DQ6(1)  
DQB1*0604 DQ6(1)  
DQB1*0605 DQ6(1)  
DQB1*06051, DQB1*06052    
DQB1*0609 DQ6(1)  
DQB1*0611 DQ1  
DQB1*06111, DQB1*06112    
DQB1*0612 DQ1  
DQB1*0614 DQ6(1)  
DQB2*0202 DQ2  
DRB1*0101 DR1  
DRB1*0102 DR1  
DRB1*01021, DRB1*01022    
DRB1*0103 DR103  
DRB1*0104 DR1  
DRB1*0301 DR17(3)  
DRB1*03011, DRB1*03012    
DRB1*0301 or DRB3*0201 DR17(3)  
DRB1*0302 DR18(3)  
DRB1*03021, DRB1*03022    
DRB1*0303 DR18(3)  
DRB1*0304 DR17(3)  
DRB1*0305 DR3  
DRB1*0306 DR3  
DRB1*0401 DR4  
DRB1*04011, DRB1*04012    
DRB1*0401 or DRB4 DR4  
DRB1*0401 or DRB4*0101 DR4  
DRB1*0402 DR4  
DRB1*0402 or DRB4 DR4  
DRB1*0404 DR4  
DRB1*04041, DRB1*04042    
DRB1*0404 or DRB4 DR4  
DRB1*0405 DR4  
DRB1*04051, DRB1*04052    
DRB1*0405 or DRB4 DR4  
DRB1*0405 or DRB4*0101 DR4  
DRB1*0406 DR4  
DRB1*0407 DR4  
DRB1*0407 or DRB4 DR4  
DRB1*0408 DR4  
DRB1*0409 DR4  
DRB1*0410 DR4  
DRB1*0411 DR4  
DRB1*0413 DR4  
DRB1*0414 DR4  
DRB1*0415 DR4  
DRB1*0416 DR4  
DRB1*0417 DR4  
DRB1*0419 DR4  
DRB1*0420 DR4  
DRB1*0421 DR4  
DRB1*0422 DR4  
DRB1*0423 DR4  
DRB1*0424 DR4  
DRB1*0425 DR4  
DRB1*0426 DR4  
DRB1*0428 DR4  
DRB1*0429 DR4  
DRB1*0701 DR7  
DRB1*0703 DR7  
DRB1*0801 DR8  
DRB1*0802 DR8  
DR*08021, DR*08022    
DRB1*08032 DR8  
DRB1*0804 DR8  
DRB1*08041, DRB1*08042,
DRB1*08043
   
DRB1*0805 DR8  
DRB1*0806 DR8  
DRB1*0807 DR8  
DRB1*0809 DR8  
DRB1*0810 DR8  
DRB1*0811 DR8  
DRB1*0812 DR8  
DRB1*0814 DR8  
DRB1*0816. DR8  
DRB1*0817 DR8  
DRB1*0901 or DRB4*0101 DR9  
DRB1*1001 DR10  
DRB1*1101 DR11(5)  
DRB1*11011, DRB1*11012,
DRB1*11013
   
DRB1*1101 or DRB3*0202 DR11(5)  
DRB1*1102 DR11(5)  
DRB1*1103 DR11(5)  
DRB1*1104 DR11(5)  
DRB1*11041, DRB1*11042    
DRB1*1105 DR11(5)  
DRB1*1106 DR11(5)  
DRB1*1107 DR11(5)  
DRB1*1108 DR11(5)  
DRB1*11081, DRB1*11082    
DRB1*1109 DR11(5)  
DRB1*1111 DR11(5)  
DRB1*1113 DR11(5)  
DRB1*1114 DR11(5)  
DRB1*1116 DR11(5)  
DRB1*1120 DR11(5)  
DRB1*1121 DR11(5)  
DRB1*1123 DR11(5)  
DRB1*1125 DR11(5)  
DRB1*1126 DR11(5)  
DRB1*1127 DR11(5)  
DRB1*1129 DR11(5)  
DRB1*1201 or DRB3 DR12(5)  
DRB1*1202 DR12(5)  
DRB1*12021, DRB1*12022    
DRB1*1203 DR12(5)  
DRB1*12032    
DRB1*1205 DR12(5)  
DRB1*1206 DR12(5)  
DRB1*1301 DR13(6)  
DRB1*1301 or DRB3*0101 DR13(6)  
DRB1*1302 DR13(6)  
DRB1*1302 or DRB3*1301 DR13(6)  
DRB1*1303 DR13(6)  
DRB1*13031, DRB1*13032    
DRB1*1304 DR13(6)  
DRB1*1305 DR13(6)  
DRB1*1306 DR13(6)  
DRB1*1307 DR13(6)  
DRB1*13071, DRB1*13072    
DRB1*1308 DR13(6)  
DRB1*1310 DR13(6)  
DRB1*1311 DR13(6)  
DRB1*1312 DR13(6)  
DRB1*1314 DR13(6)  
DRB1*1316 DR13(6)  
DRB1*1317 DR13(6)  
DRB1*1318 DR13(6)  
DRB1*1320 DR13(6)  
DRB1*1327 DR13(6)  
DRB1*1329 DR6  
DRB1*1401 DR14(6)  
DRB1*1402 DR14(6)  
DRB1*1403 DR1403  
DRB1*1404 DR1404  
DRB1*1405 DR14(6)  
DRB1*1407 DR14(6)  
DRB1*1411 DR14(6)  
DRB1*1412 DR14(6)  
DRB1*1413 DR14(6)  
DRB1*1414 DR14(6)  
DRB1*1417 DR6  
DRB1*1418 DR6  
DRB1*1419 DR14(6)  
DRB1*1420 DR14(6)  
DRB1*1421 DR13(6)  
DRB1*1426 DR14(6)  
DRB1*1427 DR14(6)  
DRB1*1429 DR14(6)  
DRB1*1501 DR15(2)  
DRB1*15011, DRB1*15012    
DRB1*1501 or DRB5*0101 DR15(2)  
DRB1*1502 DR15(2)  
DRB1*15021, DRB1*15022,
DRB1*15023
   
DRB1*1503 DR15(2)  
DRB1*1504 DR2  
DRB1*1505 DR15(2)  
DRB1*1506 DR15(2)  
DRB1*1508 DR2  
DRB1*1601 DR16(2)  
DRB1*16011, DRB1*16012    
DRB1*1602 DR16(2)  
DRB1*16021, DRB1*16022    
DRB1*1603 DR2  
DRB1*1604 DR16(2)  
DRB1*1605 DR2  
DRB3*0101 DR52  
DRB3*01011, DRB3*01012,
DRB3*01013,DRB3*0104
   
DRB3*0201 DR52  
DRB3*0202 DR52  
DRB3*0203 DR52  
DRB3*0207 DR52  
DRB3*0208 DR52  
DRB3*0301 DR52  
DRB3*0302 DR52  
DRB4*01 DR53  
DRB4*01011 DR53  
DRB4*0103 DR53  
DRB4*0103101, DRB4*01032    
DRB4*0105 DR53  
DRB5*0101 DR51  
DRB5*01011, DRB5*01012    
DRB5*0102 DR51  
DRB5*0107 DR51  
DRB5*0202 DR51