Transient overexpression of CD4 enhances allelic exclusion of T-cell receptor (TCR) alpha chains and promotes positive selection of class II-restricted TCR-transgenic thymocytes.

Dembic, Zlatko; Munthe, Ludvig A; Schenck, Karl; Mueller, Christoph; Bogen, Bjarne (1998). Transient overexpression of CD4 enhances allelic exclusion of T-cell receptor (TCR) alpha chains and promotes positive selection of class II-restricted TCR-transgenic thymocytes. Molecular immunology, 35(1), pp. 23-38. Pergamon 10.1016/s0161-5890(98)00004-2

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CD4 contributes to antigen recognition of T cells by binding to class II MHC molecules. There is heterogeneity in expression of CD4 coreceptor among CD4+CD8+ thymocytes. We have investigated whether the expression level of coreceptor influences positive selection. Thymocytes of mice expressing transgenic lambda2(315)-Ig-light-chain/I-Ed specific TCR are poorly positively selected because they fail to allelically exclude endogenous TCR alpha chain genes and because there is no skewing towards CD4. Transient overexpression of CD4 during thymocyte development, in mice transgenic for both TCR and CD4, resulted in skewing towards CD4 in the periphery, reduced rearrangement and expression of endogenous alpha-chains, and decreased levels of thymocyte RAG-1 transcripts. Kinetic BrdU labeling experiments showed that single CD4+ thymocytes developed faster, representing the predominant population even in the cortex of the double transgenic thymi. These results demonstrate that increased coreceptor expression can compensate for poorly selectable TCR, supporting avidity and instructional models for positive selection of thymocytes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie

UniBE Contributor:

Müller, Christoph (C)

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0161-5890

Publisher:

Pergamon

Language:

English

Submitter:

Christoph Müller

Date Deposited:

22 Sep 2022 12:36

Last Modified:

29 Mar 2023 23:38

Publisher DOI:

10.1016/s0161-5890(98)00004-2

PubMed ID:

9683261

BORIS DOI:

10.48350/172966

URI:

https://boris.unibe.ch/id/eprint/172966

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