Functional evidence that conserved TCR CDR alpha 3 loop docking governs the cross-recognition of closely related Peptide: Class I complexes Journal Article
| Authors: | Messaoudi, I.; Lemaoult, J.; Metzner, B. M.; Miley, M. J.; Fremont, D. H.; Nikolich-Zugich, J. |
| Article Title: | Functional evidence that conserved TCR CDR alpha 3 loop docking governs the cross-recognition of closely related Peptide: Class I complexes |
| Abstract: | The TCR recognizes its peptide:MHC (pMHC) ligand by assuming a diagonal orientation relative to the NMC helices, but it is unclear whether and to what degree individual TCRs exhibit docking variations when contacting similar pMHC complexes. We analyzed monospecific and cross-reactive recognition by diverse TCRs of an immunodominant HVH-1 glycoprotein B epitope (HSV-8p) bound to two closely related MHC class I molecules, H-2K(h) and H-2K(bm delta). Previous studies indicated that the pMHC portion likely to vary in conformation between the two complexes resided at the N-terminal part of the complex, adjacent to peptide residues 2-4 and the neighboring MHC side chains. We found that CTL clones sharing TCR beta -chains exhibited disparate recognition patterns, whereas those with drastically different TCR beta -chains but sharing identical TCR alpha CDR3 loops displayed identical functional specificity. This suggested that the CDR alpha3 loop determines the TCR specificity in our model, the conclusion supported by modeling of the TCR over the actual HSV-8:K-b crystal structure. Importantly, these results indicate a remarkable conservation in CDR alpha3 positioning, and, therefore, in docking of diverse TCR alpha beta heterodimers onto variant peptide:class I complexes, implying a high degree of determinism in thymic selection and T cell activation. |
| Keywords: | antigen; ligands; recognition; binding; crystal-structure; myelin basic-protein; repertoire; molecular mimicry; mhc class-ii; t-cell receptor; viral peptides |
| Journal Title: | Journal of Immunology |
| Volume: | 167 |
| Issue: | 2 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2001-07-15 |
| Start Page: | 836 |
| End Page: | 843 |
| Language: | English |
| ACCESSION: | WOS:000170949300030 |
| PROVIDER: | wos |
| PUBMED: | 11441090 |
| DOI: | 10.4049/jimmunol.167.2.836 |
| Notes: | Article -- Source: Wos |
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