Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the alpha 3 domain of MHC I molecules.
The alpha 1 and alpha 2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the alpha 3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CD8. CD8 is important in the selection of T cells as anti-CD8 antibody injected into perinatal mice interferes with this process. We previously used a hybrid class I molecule with the alpha 1/alpha 2 domains from Ld and the alpha 3 domain from Q7b and showed that this molecule binds an Ld-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-Ld cytotoxic T lymphocytes. In addition, positive selection of virus-specific Ld-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the alpha 1/alpha 2 domains of class I, the alpha 3 domain plays an important part in both positive and negative selection of antigen-specific cells.
Aldrich
C J
CJ
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas.
Hammer
R E
RE
Jones-Youngblood
S
S
Koszinowski
U
U
Hood
L
L
Stroynowski
I
I
Forman
J
J
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D016827:CD8 Antigens; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D007111:Immunity, Cellular; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins