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Positive and Negative Selection in the Thymus and the Thymic Paradox

Hindawi Publishing Corporation
Publication Date
DOI: 10.1155/1998/89415
  • Research Article
  • Education


Developmental Immunology, 1998, Vol. 5, pp. 161-168 Reprints available directly from the publisher Photocopying permitted by license only (C) 1998 OPA (Overseas Publishers Association) Amsterdam B.V. Published under license under the Harwood Academic Publishers imprint, part of the Gordon and Breach Publishing Group Printed in Malaysia Positive and Negative Selection in the Thymus and the Thymic Paradox JULIE N. REZA MARY A. RITTER* Department ofImmunology, Imperial College School ofMedicine, Hammersmith Hospital, Du Cane Road, London W12 ONN (Received 15 April 1997) Keywords: Thymus, thymocyte maturation, positive selection, negative selection INTRODUCTION The development of T cells occurs in the thymus, with thymocytes undergoing phenotypic changes and acquiring their repertoire for the antigen-specific T- cell receptor (TcR; Blackman et al., 1988) during their migration through this organ. The TcR are generated by random genetic rearrangements/recom- binations of V, D, and J elements, which, together with junctional diversity and novel insertions or deletion of bases at their V-D or D-J junctions, give rise to up to 109 V-D-J genes in mice (Marrack and Kappler, 1986; 1988). In the periphery, the resulting TcR interact with antigen-derived peptides presented by self-MHC on target cells. Due to the random mechanism by which they arise, however, it is possible that many of these TcR do not recognize the (antigen-presenting) self- MHC molecules or that they are autoreactive. These would be useless or even deleterious. Thus, develop- ing thymocytes must be "educated," such that they are selected according to the specificity and affinity of the TcR that they express. This education involves deletion of autoreactive cells (negative selection), and "major histocompatibility complex (MHC) restric- tion" (i.e., selection of thymocytes able to recognize self-MHC molecules, called positive selection), and relies on the concept that whereas receptor-antigen binding might cause T-c

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