HLA-restricted recognition of viral antigens in HLA transgenic mice.
Cytotoxic T lymphocytes (CTL) recognize antigen in the context of the class-I products of the major histocompatibility complex (MHC). The extensive polymorphism of class-I molecules is thought to be linked to their capacity to present a large variety of foreign antigens. Whether a single T-cell receptor (TCR) recognizes two separate epitopes (the foreign antigen and an epitope on MHC molecules), or a single epitope resulting from the combination of a foreign antigen and an MHC molecule, has not yet been resolved. In view of the differences between species in primary structure of histocompatibility antigens, it might be predicted that the TCR repertoire would evolve in concert with the diversity of MHC antigens. The mouse and human TCR repertoire would be optimally adapted to engage in productive interactions only with mouse (H-2) and human (HLA) MHC antigens respectively, especially if the more conserved features of histocompatibility antigens, in addition to foreign antigen, were seen by the TCR. Alternatively, only the most variable segments of MHC antigens might be engaged in antigen presentation and thus in interaction with the TCR. In that case, interaction between MHC plus antigen and the TCR might not necessarily be limited by species-specific features. By analysis of the T-cell response against virus-infected cells in HLA-B27/human beta 2-microglobulin double transgenic mice, we report here that the mouse T-cell repertoire is perfectly capable of using the human HLA-B27 antigen as a restriction element.
Kievits
F
F
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Department of Immunochematology, University of Amsterdam, The Netherlands.
Ivanyi
P
P
Krimpenfort
P
P
Berns
A
A
Ploegh
H L
HL
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015796:HLA-B27 Antigen; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D001613:beta 2-Microglobulin / Q000235:genetics
D000956:Antigens, Viral; D006183:H-2 Antigens; D006680:HLA Antigens; D015796:HLA-B27 Antigen; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin