T cell recognition of an engineered MHC class I molecule: Implications for peptide-independent alloreactivity

Vladimir Janković, Kristin Remus, Alberto Molano, Janko Nikolich-Zugich

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Previously, we described H-2KbW9 (KbW9), an engineered variant of the murine MHC class I molecule H-2Kb (Kb), 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 Kb and KbW9 are largely nonoverlapping in vivo. On the basis of these observations, we used KbW9 and Kb to revisit the role of peptides in alloreactive T cell recognition. We first compared Ab and TCR recognition of KbW9 and Kb. Six of six Kb-specific mAbs, directed against different parts of the molecule, recognized KbW9 well, albeit at different levels than Kb. Furthermore, KbW9 readily served as a restriction element for a peptide-specific syngeneic CTL response. Therefore, KbW9 mutation did not result in gross distortions of the TCR-interacting surface of class I, which was comparable between Kb and KbW9. Interestingly, when KbW9 was used to stimulate allogeneic T cells, it induced an infrequent CTL population that cross-reacted against Kb and was specific for peptide-independent MHC epitopes. By contrast, Kb-induced alloreactive CTLs recognized Kb in a peptide-specific manner, did not cross-react on KbW9, and were present at much higher frequencies than those induced by KbW9. Thus, induction of rare peptide-independent CTLs depended on unique structural features of KbW9, 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.

Original languageEnglish (US)
Pages (from-to)1887-1892
Number of pages6
JournalJournal of Immunology
Volume169
Issue number4
StatePublished - Aug 15 2002
Externally publishedYes

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T-Lymphocytes
Peptides
Point Mutation
Epitopes
Binding Sites
Mutation
Population

ASJC Scopus subject areas

  • Immunology

Cite this

T cell recognition of an engineered MHC class I molecule : Implications for peptide-independent alloreactivity. / Janković, Vladimir; Remus, Kristin; Molano, Alberto; Nikolich-Zugich, Janko.

In: Journal of Immunology, Vol. 169, No. 4, 15.08.2002, p. 1887-1892.

Research output: Contribution to journalArticle

Janković, Vladimir ; Remus, Kristin ; Molano, Alberto ; Nikolich-Zugich, Janko. / T cell recognition of an engineered MHC class I molecule : Implications for peptide-independent alloreactivity. In: Journal of Immunology. 2002 ; Vol. 169, No. 4. pp. 1887-1892.
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