Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes.
Memory T cells cross-reactive with epitopes encoded by related or even unrelated viruses may alter the immune response and pathogenesis of infection by a process known as heterologous immunity. Because a challenge virus epitope may react with only a subset of the T cell repertoire in a cross-reactive epitope-specific memory pool, the vigorous cross-reactive response may be narrowly focused, or oligoclonal. We show in this article, by examining human T cell cross-reactivity between the HLA-A2-restricted influenza A virus-encoded M1(58-66) epitope (GILGFVFTL) and the dissimilar Epstein-Barr virus-encoded BMLF1(280-288) epitope (GLCTLVAML), that, under some conditions, heterologous immunity can lead to a significant broadening, rather than a narrowing, of the TCR repertoire. We suggest that dissimilar cross-reactive epitopes might generate a broad, rather than a narrow, T cell repertoire if there is a lack of dominant high-affinity clones; this hypothesis is supported by computer simulation.
Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Shalyn C
SC
Clute
Yuri N
YN
Naumov
Levi B
LB
Watkin
Nuray
N
Aslan
John L
JL
Sullivan
David A
DA
Thorley-Lawson
Katherine
K
Luzuriaga
Raymond M
RM
Welsh
Roberto
R
Puzone
Franco
F
Celada
Liisa K
LK
Selin
D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002999:Clone Cells; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; C488936:M1 protein, Influenza A virus; D009842:Oligopeptides; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014763:Viral Matrix Proteins; C403195:glycyl-leucyl-cysteinyl-threonyl-leucyl-valyl-alanyl-methionyl-leucine; C448634:influenza matrix peptide (58-66)