Antigenic determinants in the N‐terminal halves of human κ‐chains; their relation to the variable region subgroups

Abstract

Antibodies directed against the variable ( V ) regions of b o t h t h e heavy and light chains are found consistently in fowl antisera to polyclonal h u m a n F(ab'),. When tested b y absorption and precipitation with K-Bence-Jones proteins of k n o w n amino acid sequences, nearly all such antisera were found to contain antibodies specific for o n e or m o r e of t h e three basic V, sequences. This result indicates t h a t a very high proportion of t h e normal K-chain population carries determinants which correspond to sequence patterns derived from analyses of pathological monoclonal proteins.Although it was possible t o determine t h e V, subgroups of some intact monoclonal immunoglobulins with antisera, t h e procedure has serious limitations. O n e of these is t h e need to absorb all antibody to VH-region antigens with suitable monoclonal A proteins; of 14 IgM proteins examined with such absorbed antisera, 8 were found t o have KI light chains, 3 were K I I I , 1 was KII, and 2 could n o t b e classified. Another limitation, which applies also t o Bence-Jones proteins, is t h e occurrence of ant igenically deficient K-chains, accounting for 10-20 ' % of t h e proteins tested. One such protein ( K I I I Rad)did not precipitate with most o f t h e anti-VKIII sera, b u t differed in only 7 positions from t h e basic KIII sequence.