Abstract: Antigenic epitopes on the SKDWSFY region (positions 57-63) of human β2-microglobulin (β2m) reacting in ELISA with polyclonaI and monoclonal human IgM rheumatoid factors (RF) as well as with monoclonal mouse IgG anti-β2m antibodies were studied after site-specific mutation of single or double β2m amino acid residues. Single site-specific mutations at lysine 58 and serine 61 produced a major decrease (50-100%) in reactivity of polyclonal IgM RF with β2m. Mutations at serine 57, tryptophane 60, and phenylalanine 62 also induced substantial decrements (25-49%) in IgM RF reactivity. β2m mutants containing double amino acid mutations including one residue outside the SKDWSFY region along with four different mutations at tryptophane 60 also often showed marked decrements in IgM RF anti-β2m reactivity. Site-specific mutations at virtually all residues within the SKDWSFY β2m region produced a major decrease in reactivity of two of three monoclonal human IgM RF. Results with nine murine IgG anti-β2m mAbs often showed an entirely different protile. Site-specific mutation of aspartic acid at position 59 produced a 50-100% decrease in binding of nine mAbs. Serine at position 61 and tyrosine at 63 also appeared to represent important residues for antigenic determinants reacting with anti-β2m mAbs. Results of mapping discrete epitopes using glycine substitution within overlapping 7-mers of β2m linear sequence compared with site-specific mutation of single β2m residues were similar in many instances, but also often showed marked differences. A marked change in antigenic contribution of single amino acid residues to β2m antigenic epitopes frequently depended on what residues were mutated to. Our findings emphasize that single residues within a small seven amino acid, solvent-accessible antigenic stretch of primary β2m sequence vary considerably in their contribution to the reactive antigenic structures for IgM RF as well as monoclonal IgG antibodies.

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   |étape=   Exploration
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   |texte=   Changes in Rheumatoid Factor and Monoclonal IgG Antibody Specificity after Site-Specific Mutations in Antigenic Region of β2-Microglobulin
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