Primary structural studies of the Qa-2 alloantigen: implications for the evolution of the MHC

Abstract

The murine major histocompatibility complex (MHC) contains a number of loci encoding cell-surface glycoproteins of molecular weight (MW) 40,000–45,000 which are non-covalently associated with β₂-microglobulin. The products of this large multigene family, collectively referred to as class I gene products, include H–2K,-D,-L and -R, which are encoded by the H–2 complex, and Qa-1, -2 and TL, encoded by the Tla region telomeric to H–2 (refs 1–5). Functional studies have shown that the H–2K, -D and -L gene products serve as important self-recognition structures in immune responses^6,7; a functional role for the other class I gene products has not been established. Tryptic peptide map comparisons and primary sequence analyses have indicated that H–2K, -D and -L are 70–85% homologous with respect to their amino acid sequences^8–10. The data, however, have failed to reveal structural features unique to gene products of a given locus. Recent tryptic peptide map comparisons of the Tla gene products, Qa-2 and TL, have shown that Qa-2, H-2K and -D are more closely related to each other than to TL^11,12. Here we present the NH₂-terminal sequence of the Qa-2 alloantigen. Our results, together with those of previous studies, show that Qa-2 has significant homology to H–2 antigens but differs in that Qa-2 molecules lack extensive polymorphism and the Qa-2 heavy chain has two additional NH₂-terminal amino acids and several critical amino acid interchanges compared with H–2 antigens.