Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin.
Changes in the antigenicity of major histocompatibility complex (MHC) class I molecules resulting from the association of bovine beta 2-microglobulin (beta 2-m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2-microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with myeloma cells and two monoclonal antibodies which required for their reactivity the presence of FCS have been further studied. One of them (CAB 297) recognized a determinant of bovine beta 2-m which is present on free molecules in solution as well as when they are associated with either mouse or bovine class I heavy chains. In contrast, the second monoclonal antibody (CBB 70) did not react with free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but only when their class I heavy chains are associated with bovine or with human beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant requires both xenogeneic beta 2-m and class I heavy chain of a given H-2 molecule. In order to precisely localize the antigenic determinant defined by this monoclonal antibody and therefore the region altered by the association of class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class I molecules. The results indicate that changes induced by the association of bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha 2 domain. These studies illustrate that MHC class I molecules exhibit a considerable conformational flexibility which could influence their ability to bind and present various peptides to the T-cell receptor.
Mouse Immunogenetics, U93 INSERM, Saint-Louis Hospital, Paris, France.
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A
Rocca
A
A
Opolski
A
A
Samaan
B
B
Frangoulis
L
L
Degos
M
M
Pla
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D002459:Cell Fusion; D000939:Epitopes; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology*; D007116:Immunization, Passive; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D051379:Mice; D008968:Molecular Conformation; D014183:Transplantation, Heterologous; D001613:beta 2-Microglobulin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006183:H-2 Antigens; D007143:Immunoglobulin Heavy Chains; D001613:beta 2-Microglobulin