Thymic selection by a single MHC/peptide ligand: autoreactive T cells are low-affinity cells

Immunity. 1999 Jan;10(1):83-92. doi: 10.1016/s1074-7613(00)80009-6.

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