Immune Netw.  2009 Dec;9(6):285-288. 10.4110/in.2009.9.6.285.

Expression Pattern of Immunoproteasome Subunits in Human Thymus

• Oh KI
• Seo JN

• KMID: 2150657
• DOI: http://doi.org/10.4110/in.2009.9.6.285

Abstract

The expression pattern of immunoproteasomes in human thymus has not been analyzed but may have important consequences during thymic selection. Here we examined the expression patterns of immunoproteasome subunits in fetal and adult thymic tissues by immunohistochemistry and found that all three subunits are expressed in both cortical and medullary stromal cells. These data suggest that thymic selection in human can be affected by peptide repertoires generated by immunoproteasomes.

Keyword

Immunoproteasome; MHC (major histocompatibility complex); Peptide; Selection

MeSH Terms

Adult
Humans
Immunohistochemistry
Stromal Cells
Thymus Gland

Figure

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  Figure 1 Thymic sections from human adults and fetuses were examined by immunohistochemistry using antibodies for three immunoproteasome subunits (LMP2, 7, 10) at maginification of ×200 (top row: A, B, C) or 400 (bottom row: D, E, F). (A, D) LMP2; (B, E) LMP7; (C, F) LMP10. Cells that appear brown are positive for immmunoreactivity. Three subunits are expressed exclusively in stromal cells such as epithelial cells and macrophages of both the cortex and medulla, but not thymocytes. Staining antibodies and magnification folds are indicated.

Reference

1. Starr TK, Jameson SC, Hogquist KA. Positive and negative selection of T cells. Annu Rev Immunol. 2003. 21:139–176.

2. Siggs OM, Makaroff LE, Liston A. The why and how of thymocyte negative selection. Curr Opin Immunol. 2006. 18:175–183.

3. Cosgrove D, Chan SH, Waltzinger C, Benoist C, Mathis D. The thymic compartment responsible for positive selection of CD4+ T cells. Int Immunol. 1992. 4:707–710.

4. Anderson G, Jenkinson EJ. Lymphostromal interactions in thymic development and function. Nat Rev Immunol. 2001. 1:31–40.

5. Kloetzel PM, Ossendorp F. Proteasome and peptidase function in MHC-class-I-mediated antigen presentation. Curr Opin Immunol. 2004. 16:76–81.

6. Früh K, Gossen M, Wang K, Bujard H, Peterson PA, Yang Y. Displacement of housekeeping proteasome subunits by MHC-encoded LMPs: a newly discovered mechanism for modulating the multicatalytic proteinase complex. Embo J. 1994. 13:3236–3244.

7. Gaczynska M, Rock KL, Spies T, Goldberg AL. Peptidase activities of proteasomes are differentially regulated by the major histocompatibility complex-encoded genes for LMP2 and LMP7. Proc Natl Acad Sci U S A. 1994. 91:9213–9217.

8. Tanaka K, Kasahara M. The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28. Immunol Rev. 1998. 163:161–176.

9. Nil A, Firat E, Sobek V, Eichmann K, Niedermann G. Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets. Eur J Immunol. 2004. 34:2681–2689.

10. Chen W, Norbury CC, Cho Y, Yewdell JW, Bennink JR. Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens. J Exp Med. 2001. 193:1319–1326.

11. Toes RE, Nussbaum AK, Degermann S, Schirle M, Emmerich NP, Kraft M, Laplace C, Zwinderman A, Dick TP, Müller J, Schönfisch B, Schmid C, Fehling HJ, Stevanovic S, Rammensee HG, Schild H. Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products. J Exp Med. 2001. 194:1–12.

12. Bandoh N, Ogino T, Cho HS, Hur SY, Shen J, Wang X, Kato S, Miyokawa N, Harabuchi Y, Ferrone S. Development and characterization of human constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies. Tissue Antigens. 2005. 66:185–194.

13. Niedermann G. Immunological functions of the proteasome. Curr Top Microbiol Immunol. 2002. 268:91–136.

14. Jameson SC, Hogquist KA, Bevan MJ. Positive selection of thymocytes. Annu Rev Immunol. 1995. 13:93–126.

15. Barton GM, Rudensky AY. Requirement for diverse, low-abundance peptides in positive selection of T cells. Science. 1999. 283:67–70.