Dominant and cryptic antigens in the MHC class I restricted T cell response across a complex minor histocompatibility barrier: analysis and mapping by elution of cellular peptides.
T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phenomenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti-BALB.B CTL always recognized three reverse phase HPLC fractions in BALB.B eluates, whether the latter were obtained from cell lysates or immunoaffinity purified class I molecules. One of these immunodominant epitopes (termed IDE-1) was H-2Db restricted, and two (termed IDE-2 and IDE-3) were H-2Kb restricted. B6 mice were immunized with spleen cells from B6 congenic mice carrying single minor H loci from BALB.B with the aim to assign IDE to given minor H loci and to investigate whether additional epitopes could be identified in the absence of the immunodominant ones. IDE-3 was found to be associated to the locus H-28; in addition five so called cryptic epitopes were defined. Induction of CTL against these epitopes required immunization with cells of the congenic strain; BALB.B spleen cells failed to immunize. One subgroup of these epitopes (those associated to H-8, H-19 and H-25) were nevertheless found to be processed and loaded in class I molecules of BALB.B cells, while there was no evidence for this for H-35 and H-36. For 10 additional congenic strains, no CTL response was detected. The results are discussed in relation to the genetic and molecular basis of minor H antigens, and mechanisms for epitope dominance operating at the level of the APC or responding T cells.
Wolpert
E
E
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Franksson
L
L
Kärre
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D015778:Minor Histocompatibility Antigens; D010455:Peptides