Contrast between class I and class II MHC-mediated differentiation of a CD4+CD8+ T cell line: implications for lineage commitment.

Abstract:

:Experiments in transgenic mice have demonstrated that thymocyte differentiation into the mature CD4+ helper or CD8+ cytotoxic T cell lineage is ultimately dependent upon the specificity of the TCR for class II or class I MHC molecules respectively. However, the initial mechanistic events involved in this process remain unclear. To address this issue, we have expressed a TCR specific for an ovalbumin peptide and the Kb class I MHC molecule in the DPK CD4+CD8+ precursor T cell line. This cell line originally expressed a TCR specific for a pigeon cytochrome c peptide and class II MHC molecules and has been shown previously to differentiate into CD4+CD8- cells upon recognition of antigen in vitro or thymic epithelial cells in vivo. Surprisingly, we find that recognition of either class I or class II MHC by these cells initiates differentiation into the CD4+ lineage and induces down-regulation of recombination associated genes. Unlike recognition of class II MHC, however, recognition of class I MHC does not induce full maturation. These results support a model in which (i) commitment to the CD4 lineage occurs prior to positive selection and (ii) CD4 lineage commitment is associated with a requirement for activation by a class II MHC-specific TCR in order to complete differentiation.

journal_name

Int Immunol

journal_title

International immunology

authors

DeKoning J,Carbone FR,Kaye J

doi

10.1093/intimm/7.4.541

subject

Has Abstract

pub_date

1995-04-01 00:00:00

pages

541-9

issue

4

eissn

0953-8178

issn

1460-2377

journal_volume

7

pub_type

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