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.
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.
Breur-Vriesendorp
B S
BS
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Vingerhoed
J
J
Kuijpers
K C
KC
van der Horst
A R
AR
de Waal
L P
LP
Kievits
F
F
Ivanyi
P
P
D000818:Animals; D000918:Antibody Specificity; D000939:Epitopes / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015796:HLA-B27 Antigen / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006639:Histidine / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014443:Tyrosine / Q000235:genetics*
D000939:Epitopes; D015796:HLA-B27 Antigen; D007518:Isoantibodies; D014443:Tyrosine; D006639:Histidine