PMID- 12897753
OWN - NLM
STAT- MEDLINE
DCOM- 20030905
LR  - 20190723
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 112
IP  - 2
DP  - 2003 Aug
TI  - Mutational analysis of major, sequential IgE-binding epitopes in alpha s1-casein, 
      a major cow's milk allergen.
PG  - 433-7
AB  - BACKGROUND: Allergy to cow's milk is common in early childhood, and no therapy 
      other than avoidance exists. In murine models of peanut allergy, immunotherapy 
      with mutated, engineered, proteins appears promising. OBJECTIVE: We sought to 
      identify the critical amino acids (AAs) for immunoglobulin E (IgE) binding within 
      the major B-cell epitopes of alpha(s1)-casein, a major cow's milk allergen. This 
      will provide the necessary information to alter the cDNA to encode a protein 
      capable of activating milk-specific T cells, but with reduced IgE-binding 
      capacity. METHODS: For mutational analysis of the IgE-binding epitopes, peptides 
      of 10-14 AAs in length were synthesized on a derivatized cellulose membrane with 
      single or multiple AA substitutions. Membranes were immunolabeled with pooled 
      sera from 15 cow's-milk-allergic patients and with 8 individual sera. RESULTS: 
      With the pooled sera, substitution of a single AA led to complete abrogation of 
      IgE binding to 2 of 8 peptides and diminished binding in the remainder. 
      Substitution of multiple AAs led to an abrogation of binding in the remaining 
      peptides. In 4 of the 8 peptides, the critical AA identified with pooled sera did 
      not result in significant reduction of IgE binding with 1 or more individual 
      patients. For these patients, other critical AAs were identified, indicating a 
      more heterogeneous pattern in IgE recognition. CONCLUSION: This study indicates 
      that single or multiple AA substitutions within IgE-binding epitopes result in 
      reduced binding of milk-specific IgE antibodies by patients' sera. However, for 
      future immunotherapeutic interventions with mutated peptides, critical AAs should 
      be evaluated with individual patient sera to determine B-cell-epitope 
      heterogeneity.
FAU - Cocco, Renata R
AU  - Cocco RR
AD  - Division of Pediatric Allergy and Immunology and the Jaffe Institute for Food 
      Allergy, Mount Sinai School of Medicine, New York, NY, USA.
FAU - Jarvinen, Kirsi-Marjut
AU  - Jarvinen KM
FAU - Sampson, Hugh A
AU  - Sampson HA
FAU - Beyer, Kirsten
AU  - Beyer K
LA  - eng
GR  - AI 24439/AI/NIAID NIH HHS/United States
GR  - AI 44236/AI/NIAID NIH HHS/United States
GR  - M01 RR00071/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Caseins)
RN  - 0 (Epitopes)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Sequence/genetics
MH  - Amino Acid Substitution
MH  - Caseins/*immunology/*metabolism
MH  - Child
MH  - Child, Preschool
MH  - *DNA Mutational Analysis
MH  - Epitopes/*genetics
MH  - Humans
MH  - Immunoglobulin E/*metabolism
MH  - Molecular Sequence Data
EDAT- 2003/08/05 05:00
MHDA- 2003/09/06 05:00
CRDT- 2003/08/05 05:00
PHST- 2003/08/05 05:00 [pubmed]
PHST- 2003/09/06 05:00 [medline]
PHST- 2003/08/05 05:00 [entrez]
AID - S0091674903015483 [pii]
AID - 10.1067/mai.2003.1617 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2003 Aug;112(2):433-7. doi: 10.1067/mai.2003.1617.