HLA function

Table 24.1 Complete listing of recognized serological and cellular HLA specificities.

A

B

C

D

DR

DQ

DP

A1

B5

B70

Cw1

Dw1

DR1

DQ1

DPw1

A2

B7

B71(70)

Cw2

Dw2

DR103

DQ2

DPw2

A203

B703

B72(70)

Cw3

Dw3

DR2

DQ3

DPw3

A210

B8

B73

Cw4

Dw4

DR3

DQ4

DPw4

A3

B12

B75(15)

Cw5

Dw5

DR4

DQ5(1)

DPw5

A9

B13

B76(15)

Cw6

Dw6

DR5

DQ6(1)

DPw6

A10

B14

B77(15)

Cw7

Dw7

DR6

DQ7(3)

A11

B15

B78

Cw8

Dw8

DR7

DQ8(3)

A19

B16

B81

Cw9(w3)

Dw9

DR8

DQ9(3)

A23(9)

B17

Bw4

Cw10(w3)

Dw10

DR9

A24(9)

B18

Bw6

Dw11(w7)

DR10

A2403

B21

Dw12

DR11(5)

A25(10)

B22

Dw13

DR12(5)

A26(10)

B27

Dw14

DR13(6)

A28

B2708

Dw15

DR14(6)

A29(19)

B35

Dw16

DR1403

A30(19)

B37

Dw17(w7)

DR1404

A31(19)

B38(16)

Dw18(w6)

DR15(2)

A32(19)

B39(16)

Dw19(w6)

DR16(2)

A33(19)

B3901

Dw20

DR17(3)

A34(10)

B3902

Dw21

DR18(3)

A36

B40

Dw22

A43

B4005

Dw23

DR51

A66(10)

B41

A68(28)

B42

Dw24

DR52

A69(28)

B44(12)

Dw25

A74(19)

B45(12)

Dw26

DR53

A80

B46 B47 B48

B50(21)

B5102

B5103

B60(40) B61(40) B62(15) B63(15) B64(14) B65(14) B67

Broad specificities are indicated in parentheses.

Figure 24.3 The increase in number of HLA alleles identified by year.

Figure 24.3 The increase in number of HLA alleles identified by year.

For example, the A*24020101 and A*24020102L alleles differ only by a single nucleotide that lies within an intron at a splice site. A*24020101 is expressed at normal levels on the cell surface; however, A*24020102L is expressed at very low levels on the cell surface due to the splice mutation.

Many new HLA alleles are reported each year (Figure 24.3). Details of the most recent advances in HLA nomenclature can be found in the latest WHO Nomenclature Committee for Factors of the HLA System Report or by accessing the IMGT/HLA Sequence Database, the official database of the Nomenclature Committee (www.ebi.ac.uk/imgt/hla).

The outstanding feature of HLA genes and the proteins encoded by the genes is the extensive polymorphism exhibited. At each of the genes, there are multiple possible variants (Tables 24.2 and 24.3). These variants are called alleles. The nucleotide sequence differences between HLA alleles at a given locus can be translated into the protein sequence and analyses of the polymorphism has demonstrated that most variation exists within the peptide-binding domains. Experimental data support this by showing that different HLA proteins can bind peptides with different sequences. Thus, one of the functions of HLA polymorphism is to allow the presentation of different peptides to the immune system. As there are six antigen-presenting 'classical' HLA molecules (HLA-A, -B, -C, -DR, -DQ, -DP), and most individuals are heterozygous for these loci; one can see that potentially each individual has 12 different HLA molecules, each of which can bind thousands of different peptides. The existence of a polymorphic polygenic antigen-presenting system gives each individual the capacity to elicit immune responses against a wide variety of protein antigens.

HLA polymorphism also varies within different populations.

Table 24.2 Number of HLA alleles and serologically defined antigens, by June 2003.

HLA gene

No. of alleles

No. of antigens

A

282

24

B

540

49

C

136

9

DRA

2

-

DRB1

342

20

DRB3

39

1

DRB4

12

1

DRB5

17

1

DQA1

20

-

DQB1

55

7

DPA1

20

-

DPB1

106

-

Variation in climate, geography and infectious agents are all factors that are considered to have influenced the evolution of HLA polymorphism, therefore it is not surprising to find that different ethnic groups display different HLA types.

Thus, HLA polymorphism functions as an advantage both at the level of an individual and population. The extreme diversity found makes it extremely likely that that someone somewhere should possess an HLA molecule that can be effective in generating an immune response against any infectious agent.

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