Antigen Presentation Secondary article to Lymphocytes Article Contents iyang Wang,Chiba Cancer Center Research Institute Chibo.lapan Takeshi Watanabe,Medical nstituteof ireultion,Kyush University,Fukuoka,opon Antigen presentation to Tand B lymphocytes by antigen-presenting cells plays a central role in the initiation and regulation of adaptive immune responses. Activation versus Nonactivation Antigen-presenting Cells reinfection with the same pathogen.This type of imm d Antigen presentation is an essential step in the initiation of their cell surfaces that bind foreign antigens B cells can r dendriti D8zahentgeuathernouioeopm8cmlbag (MHC)-independent anner.T lym cdiators to inctivate extraceather iators to inact the antigen-derived peptide fragments bound to MHC mole niereativelyhort peptde pred AP culs on th suc ofpoaise ion th Thus,antigens recognized by Tcells are usually processed s are n APCs prior to their presentation There are severa and Bcells.andare found in the skin.bone easons wny It is ad nodes,spleen and thymus.Depending on the nature of the APCs leads to physical contact between T cells and APCs antigen and the mode of ntigen presentation, APCs which allows reciprocal activation through costimulatory Tcells acquire the ability immune responses such as allergy and autoimmunity. stage of pathogen invasion before substantial replication of microorganisms can occur inside the host cells. Requirement for Antigen Presentation ls can result in the Innate immunity replication and expansion of intracellular pathogens In addition,recognition of short peptides instead of native The parasitic and bacterial infections include physical barriers Ws I cells to det tmore diversified antigen not normally expos to pathogen invasion.recognition of bacterial cell wall e prot polysacchari that activate the alternate com ction ded mes.These nonclonal immune responses (innate immu- Presentation to T Cells nity),which are the important first line of host defence hanisms do not discr more m cells can be divided into two major populations:a subse carrying the CD CD own as he prevent reinfection by the same pathogen. (CTLs).Aetivation of CD help ells in results in humoral immune responses which are associated Adaptive immunity gens by B cells I nese anub ze an resistance to the pathogen and greater responses upon facilitate phagocytosis,or by inducing eosinophilic in- ENCYCLOPEDIA OF LIFE SCIENCES/001 Nature Publishing Group/www.els.net 1Antigen Presentation to Lymphocytes Jiyang O Wang, Chiba Cancer Center Research Institute, Chiba, Japan Takeshi Watanabe, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan Antigen presentation to T and B lymphocytes by antigen-presenting cells plays a central role in the initiation and regulation of adaptive immune responses. Antigen-presenting Cells Antigen presentation is an essential step in the initiation of clonal immune responses against viral, parasitic and bacterial invasion. While B cells directly recognize native antigens in solution or presented by follicular dendritic cells (FDCs) in a major histocompatibility complex (MHC)-independent manner, T lymphocytes recognize antigen-derived peptide fragments bound to MHC mole￾cules on the surface of ‘professional’ antigen-presenting cells (APCs). APCs are a heterogeneous population that includes Langerhans cells, macrophages, dendritic cells and B cells, and are found in the skin, bone marrow, lymph nodes, spleen and thymus. Depending on the nature of the antigen and the mode of antigen presentation, APCs function to activate immunologically competent T cells, and delete or anergize self-reactive T cells. Thus, dysfunc￾tion of antigen presentation may cause disregulated immune responses such as allergy and autoimmunity. Requirement for Antigen Presentation Innate immunity The primitive host defence mechanisms against viral, parasitic and bacterial infections include physical barriers to pathogen invasion, recognition of bacterial cell wall polysaccharides that activate the alternate complement pathway, and induction of type I interferons (IFN) by double-stranded ribonucleic acid (RNA) viral geno￾mes.These nonclonal immune responses (innate immu￾nity), which are the important first line of host defence mechanisms, however, do not discriminate between different pathogens and, more importantly, fail to induce the immunological memory that functions to effectively prevent reinfection by the same pathogen. Adaptive immunity Unlike the nonclonal immune responses (innate immu￾nity), clonal adaptive immunity is characterized by specific resistance to the pathogen and greater responses upon reinfection with the same pathogen. This type of immune response is primarily dependent on the function of T and B lymphocytes, which express specific antigen receptors on their cell surfaces that bind foreign antigens. B cells can recognize native antigen, either in solution or presented by FDCs, and secrete specific antibodies which are effective mediators to inactivate extracellular pathogens. Rather than recognizing soluble antigens, T lymphocytes recog￾nize relatively short antigenic peptides presented by APCs. Thus, antigens recognized by T cells are usually processed in APCs prior to their presentation. There are several reasons why it is advantageous for lymphocytes to recognize presented antigen. Recognition of antigen on APCs leads to physical contact between T cells and APCs, which allows reciprocal activation through costimulatory molecules. T cells acquire the ability to recognize antigenic peptides derived from cytosolic proteins, which permits T cells to detect intracellular pathogen infection at an early stage of pathogen invasion before substantial replication of microorganisms can occur inside the host cells. Recognition of peptide fragments by T cells can result in the killing of infected cells or increased resistance to pathogen infection of host cells, thereby preventing the replication and expansion of intracellular pathogens. In addition, recognition of short peptides instead of native antigen allows T cells to detect more diversified antigenic residues of pathogen origin that are not normally exposed on the surface of the native proteins. Presentation to T Cells T cells can be divided into two major populations: a subset carrying the CD4 antigen, known as helper T cells, and a subset carrying the CD8, antigen, termed cytotoxic T cells (CTLs). Activation of CD4 1 helper T cells in general results in humoral immune responses which are associated with the production of specific antibodies against patho￾gens by B cells. These antibodies effectively neutralize and eliminate foreign antigens, either by activating comple￾ment and binding to FcgR receptors on macrophages to facilitate phagocytosis, or by inducing eosinophilic in￾Article Contents Secondary article . Antigen-presenting Cells . Requirement for Antigen Presentation . Presentation to T Cells . Presentation to B Cells . Anatomical Sites of Presentation . Activation versus Nonactivation ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net 1