Ex vivo characterization of allo-MHC-restricted T cells specific for a single MHC-peptide complex.
Alloreactive T cells are thought to be a potentially rich source of high-avidity T cells with therapeutic potential since tolerance to self-Ags is restricted to self-MHC recognition. Given the particularly high frequency of alloreactive T cells in the peripheral immune system, we used numerous MHC class I multimers to directly visualize and isolate viral and tumor Ag-specific alloreactive CD8 T cells. In fact, all but one specificities screened were undetectable in ex vivo labeling. In this study, we report the occurrence of CD8 T cells specifically labeled with allo-HLA-A*0201/Melan-A/MART-1(26-35) multimers at frequencies that are in the range of 10(-4) CD8 T cells and are thus detectable ex vivo by flow cytometry. We report the thymic generation and shaping of tumor Ag-specific, alloreactive T cells as well as their fate once seeded in the periphery. We show that these cells resemble their counterparts in HLA-A*0201-positive individuals, based on their structural and functional attributes.
Pittet
Mikaël J
MJ
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital, Lausanne, Switzerland.
Gati
Asma
A
Le Gal
Frederic-Anne
FA
Bioley
Gilles
G
Guillaume
Philippe
P
de Smedt
Magda
M
Plum
Jean
J
Speiser
Daniel E
DE
Cerottini
Jean-Charles
JC
Dietrich
Pierre-Yves
PY
Romero
Pedro
P
Zippelius
Alfred
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007519:Isoantigens / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D006649:Histocompatibility Antigens; D007519:Isoantigens; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta