Constitutive class I-restricted exogenous presentation of self antigens in vivo.
Ovalbumin (OVA)-specific CD8+ T cells from the T cell receptor-transgenic line OT-I (OT-I cells) were injected into unirradiated transgenic RIP-mOVA mice, which express a membrane-bound form of OVA (mOVA) in the pancreatic islet beta cells and the renal proximal tubular cells. OT-I cells accumulated in the draining lymph nodes (LN) of the kidneys and pancreas and in no other LN. They displayed an activated phenotype and a proportion entered cell cycle. Unilateral nephrectomy 7-13 d before inoculation of OT-I cells into RIP-mOVA mice allowed the injected T cells to home only to the regional LN of the remaining kidney (and pancreas), but when the operation was performed 4 h before injecting the T cells, homing to the LN of the excised kidney was evident. When the bone marrow of RIP-mOVA mice was replaced with one of a major histocompatibility haplotype incapable of presenting OVA to OT-I cells, no homing or activation was detectable. Therefore, OT-I cells were activated by OVA presented by short-lived antigen-presenting cells of bone marrow origin present in the draining LN of OVA-expressing tissue. These results provide the first evidence that tissue-associated "self" antigens can be presented in the context of class I via an exogenous processing pathway. This offers a constitutive mechanism whereby T cells can be primed to antigens that are present in nonlymphoid tissues, which are not normally surveyed by recirculating naive T cells.
Kurts
C
C
Thymus Biology Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Heath
W R
WR
Carbone
F R
FR
Allison
J
J
Miller
J F
JF
Kosaka
H
H
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D007700:Kinetics; D019041:L-Selectin / Q000378:metabolism; D037181:Lectins, C-Type; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010179:Pancreas / Q000166:cytology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D018960:Hyaluronan Receptors; D019041:L-Selectin; D037181:Lectins, C-Type; D010047:Ovalbumin; D000099192:CD69 Antigens