Antigen processing of two H2-IEd-restricted epitopes is differentially influenced by the structural changes in a viral glycoprotein.
The factors that influence the intracellular location(s) of MHC class II-restricted epitope loading remain poorly understood. We present evidence that two I-Ed-restricted epitopes of the influenza hemagglutinin (HA) molecule, termed site 1 (S1; encompassing amino acid residues 107-119) and site 3 (S3; encompassing amino acid residues 302-313), are generated in distinct endocytic compartments. By means of an epitope-specific mAb, we show that S1 becomes detectable in late endocytic/lysosomal vesicles; using a mutant cell line, we also show that the presentation of S1 is dependent upon H2-DM expression. In contrast, S3; presentation is H2-DM-independent and appears in early endosomes as a result of acid-induced structural changes in HA. Presentation of both epitopes can be made H2-DM-independent by denaturing HA and made H2-DM-dependent by preventing the acid-induced conformational changes from occurring. These findings indicate that the structural context of a given epitope can determine where it is processed.
Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107-5541, USA.
K A
KA
Chianese-Bullock
H I
HI
Russell
C
C
Moller
W
W
Gerhard
J J
JJ
Monaco
L C
LC
Eisenlohr
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism; D002451:Cell Compartmentation / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D000939:Epitopes / Q000235:genetics*; D005260:Female; D006681:HLA-D Antigens / Q000235:genetics / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism*; D016393:Lymphoma, B-Cell; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000939:Epitopes; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments