T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens.
We show here that T cell cross-reactivity between heterologous viruses influences the immunodominance of virus-specific CD8(+) T cells by two mechanisms. First, T cells specific for cross-reactive epitopes dominate acute responses to viral infections; second, within the memory pool, T cells specific for cross-reactive epitopes are maintained while those specific for non-cross-reactive epitopes are selectively lost. These findings suggest an immunological paradigm in which viral infections shape the available T cell repertoire, causing alterations in the hierarchies of both the primary and memory CD8(+) T cell responses elicited by subsequent viral infections. Thus, immunodominance is a function of the host's previous exposure to unrelated pathogens, and this may have an impact on protective immunity and immunopathology.
Brehm
Michael A
MA
Department of Pathology and Progranm in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Pinto
Amelia K
AK
Daniels
Keith A
KA
Schneck
Jonathan P
JP
Welsh
Raymond M
RM
Selin
Liisa K
LK
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000276:immunology; D010455:Peptides / Q000276:immunology; D018052:Pichinde virus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes; D009698:Nucleoproteins; D010455:Peptides; D014764:Viral Proteins