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DNA sequence of HLA-A11: Remarkable homology with HLA-A3 allows identification of residues involved in epitopes recognized by antibodies and T cells

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Abstract

The human class I alleles HLA-A11 and HLA-A3 have a well-documented history of serological cross-reactivity. This cross-reactivity suggests that they are closely related, a suggestion which is supported by the fact that the HLA-A11 and HLA-A3 genes are distinguished from all other A-locus genes by a restriction fragment length polymorphism observed in Bam HI digests. To examine the extent of sequence homology between HLA-A11 and HLA-A3, we have cloned the HLA-A11 gene and sequenced the coding regions (exons). The results reveal that HLA-A11 and HLA-A3 display the highest degree of homology reported for any pair of serologically defined class I alleles. Only nine base differences resulting in six amino acid differences were observed in exons 2–8. One of the amino acid substitutions is in the α1 domain and the other five are in the α2 domain. Comparison of this sequence with that of other human class I molecules implicates Gln62 as a critical residue involved in HLA-A11 – HLA-A3 serological cross-reactivity. In addition, the amino acid sequence allowed us to successfully predict cross-reactive recognition of HLA-A11 by cytotoxic T lymphocytes specific for a rare subtype of HLA-A3, HLA-A3.2. This result provides further support for the importance of the α2 domain residues 152 and 156 in forming determinants on class I molecules that are recognized by cytotoxic T lymphocytes.

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Abbreviations

CTL:

cytotoxic T lymphocyte

PBL:

peripheral blood lymphocyte

PHA:

phytohemagglutinin

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Authors and Affiliations

  1. Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, 20892, Bethesda, MD, USA

    Elliot P. Cowan & John E. Coligan

  2. Neuroimmunology Branch, National Institute of Neurological and Communicative Disorders and Stroke, 20892, Bethesda, MD, USA

    Mary Lou Jelachich & William E. Biddison

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  1. Elliot P. Cowan
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  2. Mary Lou Jelachich
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  3. William E. Biddison
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  4. John E. Coligan
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Cowan, E.P., Jelachich, M.L., Biddison, W.E. et al. DNA sequence of HLA-A11: Remarkable homology with HLA-A3 allows identification of residues involved in epitopes recognized by antibodies and T cells. Immunogenetics 25, 241–250 (1987). https://doi.org/10.1007/BF00404694

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