Structural diversity in the HLA‐A10 family of alleles: Correlations with serology

Abstract

The HLA-A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well-defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA-A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the alpha 1 helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition.(ABSTRACT TRUNCATED AT 250 WORDS)

HLAMatchmaker-Based Analysis of Human Monoclonal Antibody Reactivity Demonstrates the Importance of an Additional Contact Site for Specific Recognition of Triplet-Defined Epitopes

“…Elucidation of the three-dimensional structure and amino acid sequence polymorphisms has increased our understanding of how HLA epitopes are recognized by antibodies [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. This has permitted the development of an algorithm to determine donor-recipient HLA compatibility at the structural level.…”

Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy.

“…We describe in this paper the peptide motif of HLA-A29, the allele linked to BSR, a severe form of autoimmune uveitis. The length (9 aa) (34,35). Peptide motifs have been defined for HLA-A31 and -A33 (22).…”

Sequence-Based Typing of the HLA-A10/A19 Group and Confirmation of a Pseudogene Coamplified With A*3401

“…In particular, the motif of threonine at position 149 together with glutamic acid at 152 is shared by almost all A10 molecules. The only other HLA-A, HLA-B, or HLA-C molecules in which this motif has been found are the A*0203 and A*0238 subtypes of A2 [1,13].…”