T cell recognition of an engineered MHC class I molecule: Implications for peptide-independent alloreactivity Journal Article
| Authors: | Jankovic, V.; Remus, K.; Molano, A.; Nikolich-Zugich, J. |
| Article Title: | T cell recognition of an engineered MHC class I molecule: Implications for peptide-independent alloreactivity |
| Abstract: | Previously, we described H-2K(bW9) (K-bW9), an engineered variant of the murine MHC class I molecule H-2K(b) (K-b), devoid of the central anchor ("C") pocket owing to a point mutation on the floor of the peptide binding site; this substitution drastically altered selection of bound peptides, such that the peptide repertoires of K-b and K-bw9 are largely nonoverlapping in vivo. On the basis of these observations, we used K-bw9 and K-b to revisit the role of peptides in alloreactive T cell recognition. We first compared Ab and TCR recognition of K-bW9 and K-b. Six of six K-b-specific mAbs, directed against different parts of the molecule, recognized K-bW9 well, albeit at different levels than K-b. Furthermore, K-bW9 readily served as a restriction element for a peptide-specific syngeneic CTL response. Therefore, K-bW9 mutation did not result in gross distortions of the TCR-interacting surface of class 1, which was comparable between K-b and K-bW9. Interestingly, when K-bW9 was used to stimulate allogeneic T cells, it induced an infrequent CTL population that cross-reacted against K-b and was specific for peptide-independent MHC epitopes. By contrast, K-b-induced alloreactive CTLs recognized K-b in a peptide-specific manner, did not cross-react on K-bW9, and were present at much higher frequencies than those induced by K-bW9. Thus, induction of rare peptide-independent CTLs depended on unique structural features of K-bW9, likely due to the elevated floor of the peptide-binding groove and the consequent protruding position of the peptide. These results shed new light on the relationship between TCR and peptide-MHC complex in peptide-independent allorecognition. |
| Keywords: | receptor; monoclonal-antibodies; binding; crystal-structure; residues; variants; groove; histocompatibility complex-molecules; induced conformational-changes; viral peptides; h-2k(b) |
| Journal Title: | Journal of Immunology |
| Volume: | 169 |
| Issue: | 4 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2002-08-15 |
| Start Page: | 1887 |
| End Page: | 1892 |
| Language: | English |
| ACCESSION: | WOS:000177365800030 |
| PROVIDER: | wos |
| PUBMED: | 12165513 |
| DOI: | 10.4049/jimmunol.169.4.1887 |
| Notes: | Article -- Source: Wos |
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