{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:01:58Z","timestamp":1787007718845,"version":"build-2736575974"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,3,15]]},"abstract":"<jats:p>Triggering of a T cell requires interaction between its specific receptor (TCR) and a peptide antigen presented by a self\u2013major histocompatibility complex (MHC) molecule. TCR recognition of self-MHC by itself falls below the threshold of detection in most systems due to low affinity. To study this interaction, we have used a read-out system in which antigen-specific effector T cells are confronted with targets expressing high levels of MHC compared with the selecting and priming environment. More specifically, the system is based on CD8+ T cells selected in an environment with subnormal levels of MHC class I in the absence of \u03b22-microglobulin. We observe that the MHC restriction element can trigger viral peptide-specific T cells independently of the peptide ligand, provided there is an increase in self-MHC density. Peptide-independent triggering required at least four times the natural in vivo level of MHC expression. Furthermore, recognition of the restriction element at expression levels below this threshold was still enough to compensate for lack of affinity to peptides carrying alanine substitutions in major TCR contact residues. Thus, the specificity in TCR recognition and T cell activation is fine tuned by the avidity for self-MHC, and TCR avidities for peptide and MHC may substitute for each other. These results demonstrate a functional role for TCR avidity for self-MHC in tuning of T cell specificity, and support a role for cross-reactivity on \u201cself\u201d during T cell selection and activation.<\/jats:p>","DOI":"10.1084\/jem.189.6.883","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:48:33Z","timestamp":1027687713000},"page":"883-894","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Recognition of the Major Histocompatibility Complex Restriction Element Modulates CD8+ T Cell Specificity and Compensates for Loss of\u2009 T Cell Receptor Contacts with the Specific Peptide"],"prefix":"10.1084","volume":"189","author":[{"given":"Johan K.","family":"Sandberg","sequence":"first","affiliation":[{"name":"From the Microbiology and Tumor Biology Center, Karolinska Institute, S-17177 Stockholm, 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