Large, but not small, antigens require time- and temperature-dependent processing in accessory cells before they can be recognized by T cells.
We have studied if antigens of different size and structure all require processing in antigen-presenting cells of guinea-pigs before they can be recognized by T cells. The method of mild paraformaldehyde fixation was used to stop antigen-processing in the antigen-presenting cells. As a measure of antigen presentation we used the proliferative response of appropriately primed T cells during a co-culture with the paraformaldehyde-fixed and antigen-exposed presenting cells. We demonstrate that the large synthetic polypeptide antigen, dinitrophenyl-poly-L-lysine, requires processing. After an initial time-lag of 30 min this antigen is fully processed within 2 to 4 of culture at 37 degrees C. In contrast, the immunogenic heptapeptide, angiotensin III, can be presented by pre-fixed accessory cells, viz. without any prior processing. Antigen processing was found to be temperature-dependent and consequently energy-requiring. Processing is strongly inhibited by the lysosomotrophic drug, chloroquine, suggesting a lysosomal involvement in antigen processing. The existence of a minor, non-lysosomal pathway is suggested, since small amounts of antigen were processed even at 10 degrees C, at which temperature no transport to and from the lysosomes can occur.
D000805:Angiotensin III / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D002738:Chloroquine / Q000276:immunology / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000276:immunology; D005557:Formaldehyde / Q000494:pharmacology; D006168:Guinea Pigs; D007375:Interleukin-1 / Q000276:immunology; D008970:Molecular Weight; D010047:Ovalbumin / Q000276:immunology; D011107:Polylysine / Q000031:analogs & derivatives / Q000276:immunology; D011108:Polymers / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D013696:Temperature; D013997:Time Factors; D014373:Tuberculin / Q000276:immunology
D000941:Antigens; D004136:Dinitrobenzenes; D007375:Interleukin-1; D011108:Polymers; D014373:Tuberculin; C049249:dinitrophenyl-polylysine; D000805:Angiotensin III; D005557:Formaldehyde; D011107:Polylysine; D002738:Chloroquine; D010047:Ovalbumin; C003043:paraform