IDENTIFICATION OF A MAJOR I-E(K)-RESTRICTED DETERMINANT OF HEN EGG LYSOZYME - LIMITATIONS OF LYMPH-NODE PROLIFERATION STUDIES IN DEFINING IMMUNODOMINANCE AND CRYPTICITY

We have chemically analyzed the peptides presented by I-E(k) molecules after processing of hen egg lysozyme (HEL) by a murine B-lymphoma lin e or by splenocytes. In both cases, the identified peptides were deriv ed from a single region of HEL, containing the core residues 85-96 wit h heterogeneous N and C termini. This was a surprising result because this determinant had previously been described as cryptic-i.e., not pr esented Beer processing of intact HEL. Examination of the specificitie s of T hybridomas isolated after immunization with either HEL or 84-96 peptide (p84-96) provided an explanation for this controversy. Wherea s hybridomas induced by immunization with HEL responded equally well t o HEL and p84-96, those induced by peptide immunization showed a marke d preference for p84-96 over intact HEL. In other words, hybridomas is olated after p84-96 immunization responded poorly to forms of the 84-9 6 determinant produced by natural processing, leading to the possible erroneous interpretation that 84-96 is a hidden determinant. We conclu de that (i) p84-96 is efficiently presented on I-E(k) molecules after processing of HEL, (ii) the explanation for the weak lymph node respon se to this epitope after immunization with HEL lies at the level of th e T cell, not the antigen-presenting cell, and (iii) crypticity cannot be defined on the basis of T-cell proliferation studies alone.