Structural analysis of an HLA-B27 functional variant: identification of residues that contribute to the specificity of recognition by cytolytic T lymphocytes.
The structure of a variant HLA-B27 antigen, B27.2, that is distinguished from the HLA-B27.1 and HLA-B27.3 subgroups by specific cytolytic T lymphocytes has been established by comparative peptide mapping and sequence analysis. There are only three amino acid substitutions between B27.1 and B27.2: aspartate-77, threonine-80, and leucine-81 in HLA-B27.1 are changed to asparagine-77, isoleucine-80, and alanine-81 in HLA-B27.2. These changes account for their single charge difference detectable by isoelectric focusing. The three clustered substitutions of HLA-B27.2 are identical to the corresponding residues in HLA-A24, so that both molecules become identical in their amino acid sequence between residues 72 and 96. This suggests that gene conversion may have occurred during the diversification of the HLA-B27 antigens. HLA-B27.2 has no changes in the alpha 2 domain and is similar in its pattern of substitutions to the murine bm11 mutant. It is suggested that residues 77-81 are of major significance in determining the specificity of cellular recognition of class I HLA antigens. This study, together with the previous analyses of HLA-B27.1 and HLA-B27.3, completes the structural characterization of the three major HLA-B27 functional subtypes and establishes the molecular basis of their functional and serological differences.
M A
MA
Vega
A
A
Ezquerra
S
S
Rojo
P
P
Aparicio
R
R
Bragado
J A
JA
López de Castro
D000595:Amino Acid Sequence; D000939:Epitopes / Q000276:immunology; D005785:Gene Conversion; D006680:HLA Antigens / Q000032:analysis* / Q000276:immunology; D015796:HLA-B27 Antigen; D006801:Humans; D007525:Isoelectric Focusing; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D006680:HLA Antigens; D015796:HLA-B27 Antigen; D011948:Receptors, Antigen, T-Cell