An agent or combination of agents that elicits an antigen-specific tolerogenic response to an aggrecan polypeptide selected from: a) (i) an antigen that corresponds in whole or in part to an aggrecan polypeptide, or a polynucleotide encoding an antigen that corresponds in whole or in part to an aggrecan polypeptide; co-administered together with (ii) at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, or a polynucleotide encoding the at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor; or b) an antigen presenting cell to which: (i) an antigen that corresponds in whole or in part to an aggrecan polypeptide, or a polynucleotide encoding an antigen that corresponds in whole or in part to an aggrecan polypeptide; and (ii) at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, or a polynucleotide encoding at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, have been delivered ex vivo; or c) a T lymphocyte which has been contacted with the APC of (b); or d) a complex comprising an antigen that corresponds in whole or in part to an aggrecan polypeptide and a Major Histocompatibility Complex component; or e) a B cell expressing a nucleic acid molecule that encodes an antigen that corresponds in whole or in part to an aggrecan polypeptide, wherein inducing expression leads to presentation of the antigen or processed form thereof on the surface of the B cell; or f) a construct comprising an immunomodulatory peptide attached to an immune/T-cell-binding ligand (I/TCBL), wherein the immunomodulatory peptide comprises an amino acid sequence corresponding to a portion of an aggrecan polypeptide which binds to an antigen receptor on pro-inflammatory or autoreactive T lymphocytes, and wherein the I/TCBL binds to a class or subclass of T cell selected from the group consisting of helper T cells, suppressor T cells and cytotoxic T cells and modulates T cell activity; or g) an altered peptide ligand that comprises or consists of an amino acid sequence corresponding to a portion of an aggrecan polypeptide which binds to an antigen receptor on pro-inflammatory or autoreactive T lymphocytes, wherein the APL amino acid sequence is distinguished from the amino acid sequence of the portion by at least one amino acid substitution, deletion or addition, and the APL interferes with normal signaling through an antigen receptor; or h) a combination of (b) and (c), for use in treating or preventing joint damage in a human subject with early RA or incipient RA, wherein the aggrecan polypeptide is a citrullinated aggrecan polypeptide. a) (i) an antigen that corresponds in whole or in part to an aggrecan polypeptide, or a polynucleotide encoding an antigen that corresponds in whole or in part to an aggrecan polypeptide; co-administered together with (ii) at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, or a polynucleotide encoding the at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor; or (i) an antigen that corresponds in whole or in part to an aggrecan polypeptide, or a polynucleotide encoding an antigen that corresponds in whole or in part to an aggrecan polypeptide; co-administered together with (ii) at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, or a polynucleotide encoding the at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor; or b) an antigen presenting cell to which: (i) an antigen that corresponds in whole or in part to an aggrecan polypeptide, or a polynucleotide encoding an antigen that corresponds in whole or in part to an aggrecan polypeptide; and (ii) at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, or a polynucleotide encoding at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, have been delivered ex vivo; or (i) an antigen that corresponds in whole or in part to an aggrecan polypeptide, or a polynucleotide encoding an antigen that corresponds in whole or in part to an aggrecan polypeptide; and (ii) at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, or a polynucleotide encoding at least one NF-κB inhibitor, mTOR inhibitor or Syk inhibitor, c) a T lymphocyte which has been contacted with the APC of (b); or d) a complex comprising an antigen that corresponds in whole or in part to an aggrecan polypeptide and a Major Histocompatibility Complex component; or e) a B cell expressing a nucleic acid molecule that encodes an antigen that corresponds in whole or in part to an aggrecan polypeptide, wherein inducing expression leads to presentation of the antigen or processed form thereof on the surface of the B cell; or f) a construct comprising an immunomodulatory peptide attached to an immune/T-cell-binding ligand (I/TCBL), wherein the immunomodulatory peptide comprises an amino acid sequence corresponding to a portion of an aggrecan polypeptide which binds to an antigen receptor on pro-inflammatory or autoreactive T lymphocytes, and wherein the I/TCBL binds to a class or subclass of T cell selected from the group consisting of helper T cells, suppressor T cells and cytotoxic T cells and modulates T cell activity; or g) an altered peptide ligand that comprises or consists of an amino acid sequence corresponding to a portion of an aggrecan polypeptide which binds to an antigen receptor on pro-inflammatory or autoreactive T lymphocytes, wherein the APL amino acid sequence is distinguished from the amino acid sequence of the portion by at least one amino acid substitution, deletion or addition, and the APL interferes with normal signaling through an antigen receptor; or h) a combination of (b) and (c),