Fine specificity analysis of idiotype-specific suppressor factors that block a delayed-type hypersensitivity response to M315: evidence supporting a role for somatic mutations in the variable region of the lambda 2 chain of M315.

The delayed-type hypersensitivity (DTH) response in BALB/c mice to the idiotype of M315 (alpha,lambda 2), a BALB/c myeloma protein, can be suppressed by a single i.v. injection of soluble M315. This suppression involves the generation of suppressor T cells. Mice tolerized by M315 produce subcellular factors that suppress the M315-DTH response. Such suppressor factors can be obtained by mechanical disruption of spleen cells or thymocytes from mice treated i.v. with M315. The fine specificity of the factor was studied using various immunoadsorbents such as L315 and germline V lambda 2 chain-Sepharose beads with known amino acid sequences. The results indicated that the specificity of the factor depended on three contiguous somatically mutated amino acid residues, Phe94, Arg95 and Asn96, in the third hypervariable region of the V domain of the L chain of M315.