Degeneracy, mimicry and crossreactivity in immune recognition.

Degeneracy of recognition of antigen by the immune system is being used as an argument that the self-nonself discrimination cannot be a property of the specificity of its antigen-receptors, TCR and BCR, but must rely on emergent properties derived from a set of complex interactions and pathways. This essay analyzes an alternative view by showing that degeneracy and specificity are not mutually exclusive properties. The self-nonself discrimination is the sole evolutionary selection pressure for the specificity of the TCR and BCR, which can be quantitated as a "Specificity Index." Degeneracy is a non-issue for the self-nonself discrimination largely because it is a problem of chemistry, not of biology.

[1]  Z Dembic,et al.  Response to Cohn: The Immune System Rejects the Harmful, Protects the Useful and Neglects the Rest of Microorganisms , 2004, Scandinavian journal of immunology.

[2]  M. Nahm,et al.  Peptide Mimotopes of Pneumococcal Capsular Polysaccharide of 6B Serotype: A Peptide Mimotope Can Bind to Two Unrelated Antibodies1 , 2002, The Journal of Immunology.

[3]  M. Cohn Tritope model of restrictive recognition by the TCR. , 2003, Trends in immunology.

[4]  R. Meloen,et al.  Mimotopes: realization of an unlikely concept , 2000, Journal of molecular recognition : JMR.

[5]  Ohad Parnes,et al.  From interception to incorporation: degeneracy and promiscuous recognition as precursors of a paradigm shift in immunology. , 2004, Molecular immunology.

[6]  B. Evavold,et al.  Degenerate recognition of T cell epitopes: impact of T cell receptor reserve and stability of peptide:MHC complexes. , 2004, Molecular immunology.

[7]  D. Wraith,et al.  T-cell receptor degeneracy: the dog that did not bark. Adaptation of the self-reactive T-cell response to limit autoimmune disease. , 2004, Molecular immunology.

[8]  E. Sercarz,et al.  Recognition and function in a degenerate immune system. , 2004, Molecular immunology.

[9]  K. Garcia,et al.  Peptide register shifting within the MHC groove: theory becomes reality. , 2004, Molecular immunology.

[10]  T. Kieber‐Emmons,et al.  Immunization with a carbohydrate mimicking peptide augments tumor-specific cellular responses. , 2001, International immunology.

[11]  Dinakar M. Salunke,et al.  The Primary Antibody Repertoire Represents a Linked Network of Degenerate Antigen Specificities1 , 2002, The Journal of Immunology.

[12]  D. Kranz,et al.  T cell receptors: affinities, cross-reactivities, and a conformer model. , 2004, Molecular immunology.

[13]  D. Margulies,et al.  Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans. , 1996, Journal of molecular biology.

[14]  M. Cohn,et al.  The E-T (elephant-tadpole) paradox necessitates the concept of a unit of B-cell function: the protection. , 1987, Molecular immunology.

[15]  M. Cohn The self/nonself discrimination: reconstructing a cabbage from sauerkraut. , 1992, Research in immunology.

[16]  M. Cohn At the feet of the master: the search for universalities. Divining the evolutionary selection pressures that resulted in an immune system , 1998, Cytogenetic and Genome Research.

[17]  P. Allen,et al.  T cells are not as degenerate as you think, once you get to know them. , 2004, Molecular immunology.

[18]  M. Cohn,et al.  The Protection: The Unit of Humoral Immunity Selected by Evolution , 1990, Immunological reviews.

[19]  Melvin Cohn,et al.  If the immune repertoire evolved to be large, random, and somatically generated, then... , 2002, Cellular immunology.

[20]  Clemencia Pinilla,et al.  Specificity and degeneracy of T cells. , 2004, Molecular immunology.

[21]  R. Rappuoli,et al.  A Novel Mimetic Antigen Eliciting Protective Antibody to Neisseria meningitidis1 , 2001, The Journal of Immunology.

[22]  T. Kieber‐Emmons,et al.  Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery. , 2002, Trends in biotechnology.

[23]  The specificity of immunological reactions. , 2000, Molecular immunology.

[24]  Uri Hershberg,et al.  Antigen-receptor degeneracy and immunological paradigms. , 2004, Molecular immunology.

[25]  M. Cohn A new concept of immune specificity emerges from a consideration of the self-nonself discrimination. , 1997, Cellular immunology.

[26]  K. Wucherpfennig T cell receptor crossreactivity as a general property of T cell recognition. , 2004, Molecular immunology.

[27]  Melvin Cohn,et al.  The immune system: a weapon of mass destruction invented by evolution to even the odds during the war of the DNAs , 2002, Immunological reviews.