Positive selection of thymocytes
- PMID: 7612239
- DOI: 10.1146/annurev.iy.13.040195.000521
Positive selection of thymocytes
Abstract
Differentiation of alpha beta T cell receptor (TCR)-expressing T cells involves an obligatory interaction with self-major histocompatibility complex (MHC) molecules in the thymus. This process, called positive selection, both rescues thymocytes from programmed cell death and induces their differentiation into mature T cells. Another critical event in thymic development is to prevent maturation of hazardous autoreactive T cells; thus, mechanisms exist to eliminate T cells with self-reactive receptors (negative selection). How can these two pathways be distinguished? This question, which has long taxed immunologists, is more opposite because many features of the interactions in positive and negative selection are shared: Both processes are exquisitely MHC-allele specific, they involve MHC-bound peptide recognition, and employ at least some overlapping signal transduction pathways. However, resolution of this paradox has become much more feasible with the advent of powerful systems for withdrawing and reconstituting individual components involved in positive selection. This review describes recent advances in our understanding of the cells, receptors, ligands, and signaling pathways involved in this process. A pivotal part of this puzzle is the basis for discrimination between TCR ligands that induce positive vs negative selection. Recent work suggests that the peptide/MHC ligand for positive selection may bind with low avidity to the TCR. The implications of these data for the nature of T cell recognition during positive selection are discussed below.
Similar articles
-
A differential-avidity model for T-cell selection.Immunol Today. 1994 Aug;15(8):362-6. doi: 10.1016/0167-5699(94)90174-0. Immunol Today. 1994. PMID: 7916949 Review.
-
T-cell-receptor affinity and thymocyte positive selection.Nature. 1996 Jun 13;381(6583):616-20. doi: 10.1038/381616a0. Nature. 1996. PMID: 8637599
-
Thymic selection process induced by hybrid antibodies.Nature. 1988 Dec 1;336(6198):473-5. doi: 10.1038/336473a0. Nature. 1988. PMID: 3057386
-
[A study on mechanisms of thymic selection by intrathymic administration of antigenic peptides].Hokkaido Igaku Zasshi. 1997 Sep;72(5):517-28. Hokkaido Igaku Zasshi. 1997. PMID: 9363468 Japanese.
-
Role of thymic cortex-specific self-peptides in positive selection of T cells.Semin Immunol. 2010 Oct;22(5):287-93. doi: 10.1016/j.smim.2010.04.012. Epub 2010 May 26. Semin Immunol. 2010. PMID: 20510627 Review.
Cited by
-
Negative selection of thymocytes expressing the D10 TCR.Proc Natl Acad Sci U S A. 2002 May 14;99(10):6931-6. doi: 10.1073/pnas.102182499. Proc Natl Acad Sci U S A. 2002. PMID: 12011450 Free PMC article.
-
Mutation in fas ligand impairs maturation of thymocytes bearing moderate affinity T cell receptors.J Exp Med. 2003 Jul 21;198(2):349-60. doi: 10.1084/jem.20030220. Epub 2003 Jul 14. J Exp Med. 2003. PMID: 12860933 Free PMC article.
-
Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection.J Exp Med. 2006 Jan 23;203(1):165-75. doi: 10.1084/jem.20051836. Epub 2006 Jan 3. J Exp Med. 2006. PMID: 16390939 Free PMC article.
-
Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-gamma).Clin Exp Immunol. 2000 Jul;121(1):59-68. doi: 10.1046/j.1365-2249.2000.01256.x. Clin Exp Immunol. 2000. PMID: 10886240 Free PMC article.
-
Autoimmunity and asthma: The dirt on the hygiene hypothesis.Self Nonself. 2010 Apr;1(2):123-128. doi: 10.4161/self.1.2.11550. Epub 2010 Feb 15. Self Nonself. 2010. PMID: 21487514 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
