The alpha 3 domain of major histocompatibility complex class I molecules plays a critical role in cytotoxic T lymphocyte stimulation.
Allogeneic major histocompatibility complex class I molecules induce strong cytotoxic T lymphocyte (CTL) responses whereas xenogeneic molecules do not. We have tested a series of mouse/human hybrid molecules for their ability to stimulate mouse CTL. The molecules with murine alpha 3 domains consistently stimulated stronger CTL responses than those with human alpha 3 domains, independent of the species origin of the N-terminal alpha 1 or alpha 2 domains. We have found that the ability of class I molecules to induce strong cytotoxic responses correlates positively with their ability to stimulate expansion of the CD8+CD4-T cell subset. The results indicate that mouse T cells can recognize class I molecules with human alpha 1 and/or alpha 2 domains, but for efficient stimulation of these T cells it is important that the immunizing molecule contains a murine alpha 3 domain. We suggest that T cell priming requires an efficient interaction of CD8 with the class I alpha 3 domain, and this shows some species restriction.
Samberg
N L
NL
Imperial Cancer Research Fund, University College London, GB.
Scarlett
E C
EC
Stauss
H J
HJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000502:physiology*; D015234:HLA-A Antigens / Q000502:physiology*; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D051379:Mice; D011994:Recombinant Proteins; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006183:H-2 Antigens; D015234:HLA-A Antigens; D011994:Recombinant Proteins