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Mature CD4+ T cells perceive a positively selecting class II MHC/peptide complex in the periphery
P Muranski1, B Chmielowski, L Ignatowicz
1Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 8, 2000
Summary
Naive CD4+ T cells require peripheral MHC class II/peptide complexes for survival, mirroring thymic selection. Activated T cells, however, may only need these complexes for expansion, not survival.
Area of Science:
- Immunology
- T cell biology
- MHC-peptide interactions
Background:
- T cell receptor (TCR) repertoire selection occurs in the thymus via MHC-peptide interactions.
- The role of self-peptides bound to MHC in peripheral mature T cell survival is not well understood.
Purpose of the Study:
- To investigate whether self-peptides bound to MHC influence the survival of mature T cells in the periphery.
- To determine the requirements for naive and activated CD4+ T cell survival and expansion in different MHC contexts.
Main Methods:
- Transfer of naive CD4+ T cells from mice with endogenous peptides bound to MHC class II (Abwt) into mice with MHC class II bound to a single peptide (AbEp).
- Transfer of mixed naive CD4+ T cells from Abwt and AbEp mice into AbEp recipients.
- Transfer of wild-type activated CD4+ T cells into AbEp and Abwt mice.
Main Results:
- Naive CD4+ T cells from Abwt mice diminished when transferred into AbEp mice.
- In AbEp recipients, naive CD4+ T cells from Abwt mice declined while those from AbEp mice expanded.
- Activated CD4+ T cells survived in both AbEp and Abwt hosts but expanded more in Abwt hosts.
Conclusions:
- Naive CD4+ T cells require peripheral expression of MHC class II/peptide complexes that were involved in their thymic selection for survival.
- Activated CD4+ T cells may utilize these complexes primarily for expansion rather than survival.