DENDRITIC CELLS ARE THE MOST EFFICIENT IN PRESENTING ENDOGENOUS NATURALLY PROCESSED SELF-EPITOPES TO CLASS II-RESTRICTED T-CELLS

Dendritic cells (DC) are potent APCs, able to induce efficiently prima ry T cell-mediated responses to foreign Ags. To assess the efficiency of DC, as compared with other APC types, in the in vivo presentation o f self-Ags to CD4(+) T cells, we analyzed processing and presentation to class II-restricted T cells of endogenous naturally processed self- epitopes constitutively expressed by mouse APC. Mouse beta(2)-microglo bulin (m beta(2)-m) peptides corresponding to residues 26-39 and 24-36 are constitutively presented, in mice expressing m beta(2)-m, by I-A( d) and I-E(d) molecules respectively, as demonstrated by activation of m beta(2)-m-specific T cell hybridomas generated in BALB/c beta(2)-m- deficient mice. These dominant, naturally processed self-epitopes of m beta(2)-m are presented by APC from a variety of tissues, including t he thymus. To analyze the relative efficiency of different APC populat ions in the presentation of self-beta(2)-m, the ability of purified DC , macrophages, and large or small B cells to stimulate m beta(2)-m-spe cific T cell hybridomas was tested. Naturally processed self-m beta(2) -m epitopes are constitutively presented to T cells by any class II-po sitive APC tested, but with highest efficiency by splenic and thymic D C, followed by macrophages, large B cells, and small B cells. This hie rarchy of self-beta(2)-m presentation does not depend on differential processing capacity of these APC populations, and it correlates with e xpression of CTLA-4 ligands and ICAM-1 molecules, rather than with exp ression of class II molecules.