Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.

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