Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals.
The majority of maturing T lymphocytes that recognize self-antigens is eliminated in the thymus upon exposure to their target antigens. This physiological process of negative selection requires that tissue-specific antigens be expressed by thymic cells, a phenomenon that has been well studied in experimental animals. Here, we have examined the expression in human thymi of four retinal antigens, that are capable of inducing autoimmune ocular disease retinal S-antigen (S-Ag), recoverin, RPE65 and inter-photoreceptor retinoid-binding protein (IRBP)], as well as four melanocyte-specific antigens, two of which are used as targets for melanoma immunotherapy [gp100, melanoma antigen recognized by T cells 1, tyrosinase-related protein (TRP)-1 and TRP-2]. Using reverse transcription (RT)-PCR, we found that all thymic samples from the 18 donors expressed mRNA transcripts of most or all the eight tested tissue antigens. Yet, the expression of the transcripts varied remarkably among the individual thymic samples. In addition, S-Ag, RPE65 and IRBP were detected by immunostaining in rare cells in sections of human thymi by antibodies against these proteins. Quantitative real-time RT-PCR analysis revealed that the retinal antigen transcripts in the human thymus are present at trace levels, that are lower by approximately five orders of magnitude than those in the retina. Our observations thus support the notions that thymic expression is a common feature for all tissue-specific antigens and that the levels of expression play a role in determining the susceptibility to autoimmunity against these molecules.
Takase
Hiroshi
H
National Eye Institute, NIH, Building 10, Room 10N112, Bethesda, MD 20892, USA.
Yu
Cheng-Rong
CR
Mahdi
Rashid M
RM
Douek
Daniel C
DC
Dirusso
Gregory B
GB
Midgley
Frank M
FM
Dogra
Rajpreet
R
Allende
Gloria
G
Rosenkranz
Eliot
E
Pugliese
Alberto
A
Egwuagu
Charles E
CE
Gery
Igal
I
D000951:Antigens, Neoplasm; D019393:Arrestin / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins; D002675:Child, Preschool; D018076:DNA, Complementary / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D010088:Oxidoreductases / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051603:Recoverin; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D014018:Tissue Distribution; D019745:cis-trans-Isomerases; D058951:gp100 Melanoma Antigen; D000099214:Retinol-Binding Proteins, Interstitial; D000099178:Retinoid Isomerohydrolase
D000951:Antigens, Neoplasm; D019393:Arrestin; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D005136:Eye Proteins; D008074:Lipoproteins; D058965:MART-1 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010088:Oxidoreductases; D012333:RNA, Messenger; D051603:Recoverin; D012177:Retinol-Binding Proteins; D019745:cis-trans-Isomerases; D058951:gp100 Melanoma Antigen; D000099214:Retinol-Binding Proteins, Interstitial; D000099178:Retinoid Isomerohydrolase; C548667:MLANA protein, human; C548637:PMEL protein, human; C496731:RCVRN protein, human; C064056:tyrosinase-related protein-1