Functional substructure of antigen molecules.

Abstract

It has been firmly established that helper T lymphocytes respond to antigen only when it is presented in the context of class II major histocompatibility complex molecules. This has fostered the concept that the nominal antigen becomes physically associated with class II molecules on antigen-presenting cells (APCs). However, the structural components of antigen molecules that actually interact with class II molecules on APCs (agretopes) and with antigen receptors of T lymphocytes (epitopes) have not been precisely defined. This question was addressed using murine T cell clones specific for the model synthetic antigen L-tyrosine-p-azobenzenearsonate (ABA-tyr), which induces T cell responses despite its small size and simple structure, and a series of analogues of the homologous immunogen. Two experimental approaches were taken. First, APCs were pulsed with analogues and used to stimulate T cell proliferation. The patterns of stimulation segregated the clones into two specificity groups and indicated that the epitope recognized by the T cell included the arsonate group and elements of the side chain of tyrosine. Second, analogues that failed to stimulate were used to block the presentation of ABA-tyr in an effort to define the agretope. The blocking protocol involved serially pulsing APCs with analogue and with ABA-tyr prior to culturing with T cells. Compounds containing the core azo-linked ring structure blocked presentation of ABA-tyr in a dose-dependent fashion, whereas p-arsanilic acid and L-tyrosine were ineffective. The blocking was specific inasmuch as the compounds had no effect on the antigen-induced proliferative responses of unrelated T cell clones.(ABSTRACT TRUNCATED AT 250 WORDS)