Abstract
In H2-M- mice, the presence of a single peptide, CLIP, bound to MHC class II molecules generates a diverse repertoire of CD4+ cells. In these mice, typical self-peptides are not bound to class II molecules, with the result that a very high proportion of H2-M- CD4+ cells are responsive to the various peptides displayed on normal MHC-compatible APC. We show here, however, that such "self" reactivity is controlled by low-affinity CD4+ cells. These cells give spectacularly high proliferative responses but are virtually unreactive in certain other assays, e.g., skin graft rejection; responses to MHC alloantigens, by contrast, are intense in all assays. Possible explanations for why thymic selection directed to a single peptide curtails self specificity without affecting alloreactivity are discussed.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adoptive Transfer
-
Anemia, Aplastic / genetics
-
Anemia, Aplastic / immunology
-
Animals
-
Antigen-Presenting Cells / immunology
-
Antigen-Presenting Cells / metabolism
-
Bone Marrow Cells / immunology
-
Bone Marrow Cells / pathology
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism*
-
CD4-Positive T-Lymphocytes / transplantation
-
Graft Rejection / genetics
-
Graft vs Host Disease / genetics
-
HLA-D Antigens / genetics
-
Histocompatibility Antigens Class II / biosynthesis
-
Intestinal Diseases / genetics
-
Intestinal Diseases / immunology
-
Intestinal Diseases / pathology
-
Ligands
-
Lymphocyte Activation
-
Mice
-
Mice, Inbred C57BL
-
Mice, Inbred Strains
-
Mice, Knockout
-
Peptides / immunology*
-
Peptides / metabolism*
-
Receptors, Antigen, T-Cell / metabolism
-
Skin Transplantation / immunology
-
Thymus Gland / immunology
-
Thymus Gland / metabolism*
-
Thymus Gland / pathology
-
Up-Regulation / genetics
-
Up-Regulation / immunology
Substances
-
H2-M antigens
-
HLA-D Antigens
-
HLA-DM antigens
-
Histocompatibility Antigens Class II
-
Ligands
-
Peptides
-
Receptors, Antigen, T-Cell