The inter-locus recombinant HLA-B*4601 has high selectivity in peptide binding and functions characteristic of HLA-C.

Journal article

The vast majority of new human HLA class I alleles are formed by conversions between existing alleles of the same locus. A notable exception to this rule is HLA-B*4601 formed by replacement of residues 66-76 of the alpha 1 helix of B*1501 by the homologous segment of Cw*0102. This inter-locus recombination, which brings together characteristic elements of HLA-B and HLA-C structure, is shown here to influence function dramatically. Naturally processed peptides bound by B*4601 are distinct from those of its parental allotypes B*1501 and Cw*0102 and dominated by three high abundance peptides. Such increased peptide selectivity by B*4601 is unique among HLA-A,B,C allotypes. For other aspects of function, presence of the small segment of HLA-C-derived sequence in an otherwise HLA-B framework converts B*4601 to an HLA-C-like molecule. Alloreactive cytotoxic T lymphocytes (CTL), natural killer (NK) cells, and cellular glycosidases all recognize B*4601 as though it were an HLA-C allotype. These unusual properties are those of an allotype which has frequencies as high as 20% in south east Asian populations and is associated with predisposition to autoimmune diseases and nasopharyngeal carcinoma.

Authors: Barber, L; Percival, L; Valiante, N; Chen, L; Lee, C

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 184
• Issue: 2
• Pages: 735-740
• Publication date: 1996-08-01
• DOI: 10.1084/jem.184.2.735
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Protein Binding; Recombination, Genetic; Models, Molecular; Genes, MHC Class I; Amino Acid Sequence; Structure-Activity Relationship; T-Lymphocytes, Cytotoxic; Protein Structure, Tertiary; HLA-C Antigens; Cells, Cultured; Transfection; Molecular Sequence Data; Peptides; HLA-B Antigens; Humans; Killer Cells, Natural