On 2017 Sep 27, Donald Forsdyke commented:

"CLOSE TO SELF" AND "NEAR SELF"

A major conclusion of this elegant modeling study is that "TCR selection against self-peptides has a minimal influence on the recognition of peptides which are 'close' to self." Thus, "TCR negative selection by host peptides has only a weak suppressive effect on detecting peptides which closely resemble self." This agrees with a somewhat less elegant modeling study that invoked lymphocyte clones selected for anti-"near-self" immune reactivity. These would normally have escaped negative selection (i.e. would have been positively selected; 1). The "near-self" viewpoint contrasted with the then prevailing "altered self" viewpoint (2). However, whereas George et al. (2017) regard their study as "empirical," the earlier study (1) arose from consideration of alloreactive phenomena and recognized implications for cancer immunotherapy in keeping with an "overall objective of optimizing CRL therapy" (3, 4). Full historical reviews are available (5, 6).

1. 1.Forsdyke DR (1975) Further implications of a theory of immunity. J Theor Biol 52: l87-l98.Forsdyke DR, 1975

2. 2.Forsdyke DR (2005) "Altered-self" or "near-self" in the positive selection of lymphocyte repertoires? Immunol Lett 100: 103-106.Forsdyke DR, 2005

3. 3.Forsdyke (1977) Grant application

4. 4.Forsdyke DR (1999) Heat shock proteins as mediators of aggregation-induced "danger" signals: implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cel1s. Cell Stress Chaperone 4: 205-210.Forsdyke DR, 1999

5. 5.Forsdyke DR (2012) Immunology (1955-1975): The natural selection theory, the two signal hypothesis and positive repertoire selection. J Hist Biol 45: 139-161.Forsdyke DR, 2012

6. 6.Forsdyke DR (2015) Lymphocyte repertoire selection and intracellular self/not-self discrimination: historical overview. Immun Cell Biol 93: 297-304.Forsdyke DR, 2015

On 2017 Sep 27, Donald Forsdyke commented:

"CLOSE TO SELF" AND "NEAR SELF"

A major conclusion of this elegant modeling study is that "TCR selection against self-peptides has a minimal influence on the recognition of peptides which are 'close' to self." Thus, "TCR negative selection by host peptides has only a weak suppressive effect on detecting peptides which closely resemble self." This agrees with a somewhat less elegant modeling study that invoked lymphocyte clones selected for anti-"near-self" immune reactivity. These would normally have escaped negative selection (i.e. would have been positively selected; 1). The "near-self" viewpoint contrasted with the then prevailing "altered self" viewpoint (2). However, whereas George et al. (2017) regard their study as "empirical," the earlier study (1) arose from consideration of alloreactive phenomena and recognized implications for cancer immunotherapy in keeping with an "overall objective of optimizing CRL therapy" (3, 4). Full historical reviews are available (5, 6).

1. 1.Forsdyke DR (1975) Further implications of a theory of immunity. J Theor Biol 52: l87-l98.Forsdyke DR, 1975

2. 2.Forsdyke DR (2005) "Altered-self" or "near-self" in the positive selection of lymphocyte repertoires? Immunol Lett 100: 103-106.Forsdyke DR, 2005

3. 3.Forsdyke (1977) Grant application

4. 4.Forsdyke DR (1999) Heat shock proteins as mediators of aggregation-induced "danger" signals: implications of the slow evolutionary fine-tuning of sequences for the antigenicity of cancer cel1s. Cell Stress Chaperone 4: 205-210.Forsdyke DR, 1999

5. 5.Forsdyke DR (2012) Immunology (1955-1975): The natural selection theory, the two signal hypothesis and positive repertoire selection. J Hist Biol 45: 139-161.Forsdyke DR, 2012

6. 6.Forsdyke DR (2015) Lymphocyte repertoire selection and intracellular self/not-self discrimination: historical overview. Immun Cell Biol 93: 297-304.Forsdyke DR, 2015