To monitor conformational changes in MHC class I structure induced by interaction with peptide or β2-microglobulin (β2-m), we have taken a serologic approach. Previous studies by us and others have defined circumstances wherein specific peptides can decrease serologic recognition of class I molecules. However, such blocking of serologic epitopes has often been interpreted as steric hindrance by peptide side chains. In this paper, we describe peptide-induced gains in recognition by mAbs 30-5-7, 34-1-2, and B22/249. In experiments with mAb 30-5-7, impaired reactivity, which resulted from an L(d) loop mutation, was specifically rescued by the binding of a β- galactosidase-derived peptide to the L(d) mutant. In studies with mAb 34-1- 2, poor L(d) detection was enhanced by mutations in L(d) at β2-m interaction sites or by changes within the peptide-binding groove. To evaluate whether known peptides in the L(d) groove could influence 34-1-2 recognition, we tested six peptide ligands, four of which increased the reactivity of 34-1-2 with the L(d)-expressing cell to various degrees (up to 14-fold). It is of interest that L(d) mutations at position 9 and 95/97 made significant differences in the ranking of the peptides in regard to their ability to increase recognition by 34-1-2 and B22/249. This finding suggests that mutations in the binding groove can alter peptide conformation and result in secondary changes in class I structure. On the basis of the cumulative serologic data, we propose that the class I molecule displays considerable fluidity, and is structurally influenced by both β2-m and peptide.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1995|
ASJC Scopus subject areas
- Immunology and Allergy