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Genetically controlled immune responses of inbred mouse strains to conjugates of the ordered peptides (Tyr‐Tyr‐Glu‐Glu) and (Tyr‐Glu‐Tyr‐Glu) with multichain poly‐ DL ‐alanine as compared with the response to the random (T, G)‐A‐‐L

1975; Wiley; Volume: 5; Issue: 12 Linguagem: Inglês

10.1002/eji.1830051212

1521-4141

Michal Schwartz, Edna Mozes, Michael Sela,

Biopolymer Synthesis and Applications

Abstract In previous studies we have shown that the immune response of different inbred mouse strains to the ordered synthetic antigen (Tyr‐Tyr‐Glu‐Glu)‐A‐‐L is similar to that observed with the random polypetide (T, G)‐A‐‐L in the pattern of response and in the cross‐reactivity of specific antibodies with it. By inhibition studies of the hemolytic plaque‐forming cell (PFC) assay we have now further confirmed that T‐T‐G‐G is the major determinant in the random (T, G)‐A‐‐L. C3H/HeJ mice were found to be nonresponders to (T‐T‐G‐G)‐A‐‐L, whereas using the same techniques these mice produced low titers of antibodies to the random (T, G)‐A‐‐L. Using the hemolytic PFC technique low numbers of antibody‐producing cells were detected in spleens of C3H/HeJ mice. However, the avidity of these antibodies as measured by inhibition of PFC was low as compared with that observed for antibody produced in C3H.SW mice in response to the ordered (Tyr‐Tyr‐Glu‐Glu)‐A‐‐L. Genetic analysis experiments demonstrated a close linkage between the ability to respond to (Tyr‐Tyr‐Glu‐Glu)‐A‐‐L and the major histocompatibility locus (H‐2) of the mouse as was previously shown for (T, G)‐A‐‐L. In contrast, no linkage was observed between the immune response potential to (Tyr‐Glu‐Tyr‐Glu)‐A‐‐L and the H‐2 as indicated by the pattern of response of different inbred and congenic mouse strains and by genetic analysis. Thus, the change in the order of two amino acid residues within the sequence of the tetrapeptide caused an enormous change in the biological specificity of the antibodies produced and in the genetic control of the immune response.