The importance of pairwise interactions between peptide residues in the delineation of TCR specificity

Leggatt, G. R., Hosmalin, A., Pendleton, C. D., Kumar, A., Hoffman, S. and Berzofsky, J. A. (1998) The importance of pairwise interactions between peptide residues in the delineation of TCR specificity. Journal of Immunology, 161 9: 4728-4735.

Author Leggatt, G. R.
Hosmalin, A.
Pendleton, C. D.
Kumar, A.
Hoffman, S.
Berzofsky, J. A.
Title The importance of pairwise interactions between peptide residues in the delineation of TCR specificity
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 1998-11
Sub-type Article (original research)
Volume 161
Issue 9
Start page 4728
End page 4735
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
A minimal, nonamer epitope (TEMEKEGKI) from the reverse transcriptase protein of HIV-1, restricted by H-2K(k), was ideatified and the function of individual residues determined. Besides classical anchor residues at positions 2 and 9, methionine at position 3 was identified as an important MHC anchor and improved binding of a different (malarial) nonamer epitope to H-2K(k), albeit while also abolishing CTL recognition. Lysine at position 5 was replaceable by alanine for CTL raised against wild-type peptide but abolished recognition for CTL raised against the variant 5ALA peptide, indicating a unidirectional cross-reactivity. Interestingly, one CTL line raised against the 5ALA substituted peptide was permissive for a double substitution at positions 5 and 6, in which lysine was permissive at position 5 only if the adjacent glutamic acid was replaced by alanine. Extensive analysis revealed three distinct patterns of responses with peptides doubly substituted in this region: recognition of both single substitutions but not the double substitution, recognition of only one single substitution but also the double substitution, or recognition of both single substitutions and the double substitution. A second complementary substitution can therefore restore function lost through a first substitution. Thus, no residue acts independently of its neighbors, and pairs of substitutions may give results not predictable from the effects of each taken singly. This finding may have bearing on viral infections (such as HIV), in which the accumulation of two mutations in the epitope may lead to the reengagement of memory CTL previously silenced by the initial mutation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Wed, 09 Mar 2011, 13:01:05 EST