Effect of a Tyr-to-His Point-mutation at Position 59 in the Alpha-1 Helix of the HLA-B27 Class-I Molecule on Allospecific and Virus-specific Cytotoxic T-lymphocyte Recognition

Abstract

HLA-B2703, a mutation of HLA-B2705, is characterized by a Tyr-to-His substitution at position 59 in the alpha 1 domain of the class-I heavy chain. So far, the HLA-B2703 subtype was found only in two Black individuals and it is the first polymorphism at position 59 of MHC class-I molecules. We have examined whether the single amino-acid substitution at position 59 results in an alloantigenic determinant and HLA-restriction element, and whether HLA-B2703 functionally differs from HLA-B2705. In vitro, HLA-B2703-positive lymphocytes were not stimulated by HLA-B2705-positive cells. Nevertheless, HLA-B2703 was recognized as an alloantigen. HLA-B2702-anti-HLA-B2705 CTL lysed HLA-B2703-positive cells less efficiently than HLA-B2705-positive cells. In addition, anti-HLA-B27 antibodies were found that lysed HLA-B2705 but not HLA-B2703 positive cells. Also, CTL clones have been described that can distinguish HLA-B2703 from HLA-B2705 (1). However, the HLA-B2703 subtype did not function as a private virus restriction element. HLA-B2705-restricted influenza virus-specific CTL also recognized HLA-B2703-positive virus-infected cells, and vice versa.

Thus, the HLA-B2703 mutation represents an example of a class-I antigen without specific significance for the recognition of viral peptides.

Key Words:

• HLA-B27
• polymorphism
• cytotoxic T lymphocytes