Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) δ1 (CDR3δ1) Determine the Structure and Function of TCRγ4δ1

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 May 25

PMID 21606499

Citations 1

Authors

Yan Jiang

Yang Guo

Xueyan Xi

Lianxian Cui

Wei He

Affiliations

Soon will be listed here.

Abstract

The γδ T cell receptor (TCR) differs from immunoglobulin and αβ TCR in its overall binding mode. In human, genes δ1, δ2, and δ3 are used for TCRδ chains. Previously, we have studied antigen binding determinants of TCRδ2 derived from dominant γδ T cells residing in peripheral blood. In this study we have investigated the critical determinants for antigen recognition and TCR function in TCRδ1 originated from gastric tumor-infiltrating γδ T lymphocytes using three independent experimental strategies including complementary determining region 3 (CDR3) of TCRδ1 (CDR3δ1)-peptide mediated binding, CDR3δ1-grafted TCR fusion protein-mediated binding, and TCRγ4δ1- and mutant-expressing cell-mediated binding. All three approaches consistently showed that the conserved flanking V and J sequences but not the diverse D segment in CDR3δ1 determine the antigen binding. Most importantly, we found that mutations in the V and J regions of CDR3δ1 also abolish the assembly of TCR and TCR-CD3 complexes in TCRγ4δ1-transduced J.RT3-T3.5 cells. Together with our previous studies on CDR3δ2 binding, our finding suggests that both human TCRδ1 and TCRδ2 recognize antigen predominately via flanking V and J regions. These results indicate that TCRγδ recognizes antigens using conserved parts in their CDR3, which provides an explanation for a diverse repertoire of γδTCRs only recognizing a limited number of antigens.

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References

Jones S, Peng P, Yang S, Hsu C, Cohen C, Zhao Y . Lentiviral vector design for optimal T cell receptor gene expression in the transduction of peripheral blood lymphocytes and tumor-infiltrating lymphocytes. Hum Gene Ther. 2009; 20(6):630-40. PMC: 2828626. DOI: 10.1089/hum.2008.048. View

Scotet E, Martinez L, Grant E, Barbaras R, Jeno P, Guiraud M . Tumor recognition following Vgamma9Vdelta2 T cell receptor interactions with a surface F1-ATPase-related structure and apolipoprotein A-I. Immunity. 2005; 22(1):71-80. DOI: 10.1016/j.immuni.2004.11.012. View

Kabelitz D, Marischen L, Oberg H, Holtmeier W, Wesch D . Epithelial defence by gamma delta T cells. Int Arch Allergy Immunol. 2005; 137(1):73-81. DOI: 10.1159/000085107. View

Sun Z, Kim K, Wagner G, Reinherz E . Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer. Cell. 2001; 105(7):913-23. DOI: 10.1016/s0092-8674(01)00395-6. View

Chung S, Strominger J . Regulation of T-cell antigen receptor (TCR) alpha-chain expression by TCR beta-chain transcripts. Proc Natl Acad Sci U S A. 1995; 92(9):3712-6. PMC: 42031. DOI: 10.1073/pnas.92.9.3712. View

Falini B, Flenghi L, Pileri S, Pelicci P, Fagioli M, Martelli M . Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues. J Immunol. 1989; 143(8):2480-8. View

Konigshofer Y, Chien Y . Gammadelta T cells - innate immune lymphocytes?. Curr Opin Immunol. 2006; 18(5):527-33. DOI: 10.1016/j.coi.2006.07.008. View

Das H, Wang L, Kamath A, Bukowski J . Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates. Blood. 2001; 98(5):1616-8. DOI: 10.1182/blood.v98.5.1616. View

Wu J, Groh V, Spies T . T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial gamma delta T cells. J Immunol. 2002; 169(3):1236-40. DOI: 10.4049/jimmunol.169.3.1236. View

10.

Constant P, Davodeau F, Peyrat M, Poquet Y, Puzo G, Bonneville M . Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994; 264(5156):267-70. DOI: 10.1126/science.8146660. View

11.

Klausner R, Lippincott-Schwartz J, Bonifacino J . The T cell antigen receptor: insights into organelle biology. Annu Rev Cell Biol. 1990; 6:403-31. DOI: 10.1146/annurev.cb.06.110190.002155. View

12.

Yaacob N, Hamzah N, Nik Mohamed Kamal N, Zainal Abidin S, Lai C, Navaratnam V . Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro. BMC Complement Altern Med. 2010; 10:42. PMC: 2924269. DOI: 10.1186/1472-6882-10-42. View

13.

Adams E, Chien Y, Garcia K . Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22. Science. 2005; 308(5719):227-31. DOI: 10.1126/science.1106885. View

14.

Shin S, El-Diwany R, Schaffert S, Adams E, Garcia K, Pereira P . Antigen recognition determinants of gammadelta T cell receptors. Science. 2005; 308(5719):252-5. DOI: 10.1126/science.1106480. View

15.

Peng G, Wang H, Peng W, Kiniwa Y, Seo K, Wang R . Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity. 2007; 27(2):334-48. DOI: 10.1016/j.immuni.2007.05.020. View

16.

Groh V, Steinle A, Bauer S, Spies T . Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science. 1998; 279(5357):1737-40. DOI: 10.1126/science.279.5357.1737. View

17.

Xu B, Pizarro J, Holmes M, McBeth C, Groh V, Spies T . Crystal structure of a gammadelta T-cell receptor specific for the human MHC class I homolog MICA. Proc Natl Acad Sci U S A. 2011; 108(6):2414-9. PMC: 3038733. DOI: 10.1073/pnas.1015433108. View

18.

Schondelmaier S, Wesch D, Pechhold K, Kabelitz D . V gamma gene usage in peripheral blood gamma delta T cells. Immunol Lett. 1993; 38(2):121-6. DOI: 10.1016/0165-2478(93)90176-3. View

19.

Morita C, Jin C, Sarikonda G, Wang H . Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev. 2007; 215:59-76. DOI: 10.1111/j.1600-065X.2006.00479.x. View

20.

Wang H, Fang Z, Morita C . Vgamma2Vdelta2 T Cell Receptor recognition of prenyl pyrophosphates is dependent on all CDRs. J Immunol. 2010; 184(11):6209-22. PMC: 3069129. DOI: 10.4049/jimmunol.1000231. View