Limited clonality in autoimmunity: Drivers and regulators

Peter Van Den Elzen, Juscilene S. Menezes, Akio Ametani, Emanual Michael Maverakis, Loui Madakamutil, Xiao Lei Tang, Vipin Kumar, Eli E. Sercarz

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The available T cell repertoire directed against self is appreciable owing to the escape of many clones from negative selection, largely because many determinants on self proteins are cryptic and not presented adequately. In addition, the degeneracy of T cell receptor specificity permits each lymphocyte a broad recognitive potential. Within the available self-reactive repertoire are T cells with high affinity, and these can compete favorably with other T cells with the same specificity. We have studied a "driver clone" and its two specific regulators in the B10.PL model of experimental autoimmune encephalomyelitis and found that each of these repertoires is highly limited. There is a single major clonal family comprising the aggressive driver population, which is public and of high affinity, and just one other minor public clonotype. The receptors of this Vβ8.2/Jβ2.7 driver are presented to a CD4 regulator and a CD8 suppressor, each of limited clonality, the latter killing the driver clone by apoptosis, completing a feedback control loop. This tightly regulated group of three cell types furnishes an excellent example of the immune homunculus.

Original languageEnglish (US)
Pages (from-to)524-529
Number of pages6
JournalAutoimmunity Reviews
Volume3
Issue number7-8 SPEC.ISS.
DOIs
StatePublished - Nov 2004
Externally publishedYes

Keywords

  • Antigen processing
  • Competition
  • Degeneracy of T cell receptor recognition
  • Driver clones
  • Immune homunculus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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