On the role of high- and low-abundance class II MHC-peptide complexes in the thymic positive selection of CD4(+) T cells.
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.
Chmielowski
B
B
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Muranski
P
P
Kisielow
P
P
Ignatowicz
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell; D013950:Thymus Gland / Q000276:immunology*
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C117647:antigenic peptide Ealpha52-68; C045084:invariant chain