INJECTION OF DETERGENT-DENATURED OVALBUMIN PRIMES MURINE CLASS I-RESTRICTED CYTOTOXIC T-CELLS IN-VIVO

Complex adjuvant formulations have been used to introduce soluble protein antigens into the ''endogenous'' processing pathway and hence to elicit specific, major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) responses. We tested if simple modifications of a model protein antigen, i. e. ovalbumin (OVA), can render it immunogenic for murine class I-restricted CTL when injected into mice in soluble form. Injection of 1-100 mu g native OVA into C57BL/6 (H-2(b)) mice did not stimulate a class I-restricted CTL response. In contrast, immunization of mice with 0.5 to 10 mu g sodium dodecyl sulfate (SDS)- or deoxycholate (DOC)-denatured OVA efficiently primed CD8(+) CTL specific for the well-characterized K-b-restricted OVA(257-264) epitope. Gel-purified SDS-denatured OVA devoid of protein fragments and excess detergent efficiently stimulated a specific CTL response in vivo. OVA preparations denatured by heat or urea treatment were not immunogenic for murine CTL. Injection of non-treated or detergent-treated, antigenic OVA(257-264) peptide into mice did not elicit a CTL response. Thus, denaturation of OVA by simple detergents such as SDS or DOC dramatically enhances its immunogenicity for class I-restricted CTL but not all modes of denaturation are equally effective.