On the role of high- and low-abundance class II MHC-peptide complexes in the thymic positive selection of CD4(+) T cells

Int Immunol. 2000 Jan;12(1):67-72. doi: 10.1093/intimm/12.1.67.

Abstract

The role of self-peptides bound to MHC molecules in the selection of T cells in the thymus remains controversial. Here, we have tested whether a high-abundance single class II MHC-peptide complex has a dominant effect on the repertoire of CD4(+) T cells selected by low-abundance class II MHC-peptide complexes. For these studies, we have used H-2(b) mice that lack an invariant chain (Ii) (A(b)Ii(-)) and their transgenic variant (A(b)A(b)EpIi(-)) that co-expresses A(b) molecules covalently bound with a single peptide Ep(52-68). In these latter mice, close to 50% of all A(b) molecules are occupied by Ep(52-68) peptide. Although the A(b)Ep complex was abundantly expressed in the thymus under conditions excluding negative selection on bone marrow-derived cells, no striking quantitative difference between repertoires of TCR expressed on CD4(+) T cells in A(b)Ii(-) and A(b)A(b)EpIi(-) mice was noticed. Our results are consistent with the view that diverse, low-abundance self-peptides play an important role in thymic positive selection and do not support the notion that dominant, high-abundance peptides may be critical for shaping the TCR repertoire.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Surface
  • CD4-Positive T-Lymphocytes / immunology*
  • Gene Rearrangement, T-Lymphocyte*
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Peptide Fragments*
  • Peptides / immunology*
  • Receptors, Antigen, T-Cell*
  • Thymus Gland / immunology*

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Antigens, Surface
  • Histocompatibility Antigens Class II
  • Peptide Fragments
  • Peptides
  • Receptors, Antigen, T-Cell
  • antigenic peptide Ealpha52-68
  • invariant chain