The T lymphocyte response to syngeneic λ2 light chain idiotopes. Significance of individual amino acids revealed by variant λ2 chains and idiotope‐mimicking chemically synthesized peptides

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Abstract
In the present study we have investigated the structure of the helper T cell (Th)-defined idiotope (Id) of myeloma protein 315 λ2 light chain (λ2315) in BALB/c (H-2d) mice which carry a high-responder immune response gene for this Id. Three eptides were synthesized which spanned the third hypervariable region (HV3) of λ2315: peptides 88–99, 94–108 and 91–108. Only peptide 91–108 was capable of eliciting carrier-specific Th that recognized M315 or free λ2315. These Th did not recognize λ25–7 chain which differs from λ2315 at 4 positions in this region; these are Tyr94, Ser95, Thr96, Tyr98 for λ25–7 and Phe94, Arg95, Asn96, Phe98 for λ2315. Immunization with peptide analogues revealed that substitution of Tyr for Phe94 was compatible with Id-λ2315 mimicry, but substitution of Ser for Arg95 or Thr for Asn96 destroyed the Th-recognized Id. Furthermore, Th primed with λ25–7 chain did not cross-react with λ2T952 these λ2 chains only differ from each other at positions 98 and 99 at the Vλ2-Jλ2 junction. The data indicate that individual amino acids of short peptide segments are critical for Th-recognized Id of the λ2 HV3 loop and Vλ2-Jλ2 junction. Furthermore, the immunogenicity of a small peptide suggests that the carrier (λ2)-specific Th recognize Id that have been processed by antigen-presenting cells (APC). This implies the existence of two categories of “internal images” of foreign or of self antigens: (a) serologically defined and (b) T lymphocyte defined. We propose that as a rule, Id processing by APC, including B cells, destroys the first and reveals the second category. The possible physiological function of these Id-specific T cells in network interactions with B cells is discussed.